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Educating Students about the Immune System, Diseases and Vaccines

Vaccine education center.

Visit the Vaccine Makers Project website to find:

• Lessons for students from elementary school through high school and college
• Materials that are aligned to the Next Generation Science Standards (NGSS) and Common Core State Standards (CCSS)
• Videos and 3-D animations to use in the classroom

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family's personal health. You should not use it to replace any relationship with a physician or other qualified healthcare professional. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult your physician or, in serious cases, seek immediate assistance from emergency personnel.

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Vaccines and immunization: What is vaccination?

Vaccination is a simple, safe, and effective way of protecting you against harmful diseases, before you come into contact with them. It uses your body’s natural defenses to build resistance to specific infections and makes your immune system stronger.

Vaccines train your immune system to create antibodies, just as it does when it’s exposed to a disease. However, because vaccines contain only killed or weakened forms of germs like viruses or bacteria, they do not cause the disease or put you at risk of its complications.

Most vaccines are given by an injection, but some are given orally (by mouth) or sprayed into the nose.

Vaccines reduce risks of getting a disease by working with your body’s natural defenses to build protection. When you get a vaccine, your immune system responds. It:

Recognizes the invading germ, such as the virus or bacteria.

Produces antibodies. Antibodies are proteins produced naturally by the immune system to fight disease.

Remembers the disease and how to fight it. If you are then exposed to the germ in the future, your immune system can quickly destroy it before you become unwell.

The vaccine is therefore a safe and clever way to produce an immune response in the body, without causing illness.

Our immune systems are designed to remember. Once exposed to one or more doses of a vaccine, we typically remain protected against a disease for years, decades or even a lifetime. This is what makes vaccines so effective. Rather than treating a disease after it occurs, vaccines prevent us in the first instance from getting sick.

Vaccines protect us throughout life and at different ages, from birth to childhood, as teenagers and into old age. In most countries you will be given a vaccination card that tells you what vaccines you or your child have had and when the next vaccines or booster doses are due. It is important to make sure that all these vaccines are up to date.

If we delay vaccination, we are at risk of getting seriously sick. If we wait until we think we may be exposed to a serious illness – like during a disease outbreak – there may not be enough time for the vaccine to work and to receive all the recommended doses.

If you have missed any recommended vaccinations for you or your child, talk to your healthcare worker about catching up.

Without vaccines, we are at risk of serious illness and disability from diseases like measles, meningitis, pneumonia, tetanus and polio. Many of these diseases can be life-threatening. WHO estimates that childhood vaccines alone save over 4 million lives every year.

Although some diseases may have become uncommon, the germs that cause them continue to circulate in some or all parts of the world. In today’s world, infectious diseases can easily cross borders, and infect anyone who is not protected

Two key reasons to get vaccinated are to protect ourselves and to protect those around us. Because not everyone can be vaccinated – including very young babies, those who are seriously ill or have certain allergies – they depend on others being vaccinated to ensure they are also safe from vaccine-preventable diseases.

• Cervical cancer
• Ebola virus disease
• Hepatitis B
• Japanese encephalitis
• Yellow fever

Some other vaccines are currently under development or being piloted, including those that protect against Zika virus or malaria, but are not yet widely available globally.

Not all of these vaccinations may be needed in your country. Some may only be given prior to travel, in areas of risk, or to people in high-risk occupations. Talk to your healthcare worker to find out what vaccinations are needed for you and your family.

Nearly everyone can get vaccinated. However, because of some medical conditions, some people should not get certain vaccines, or should wait before getting them. These conditions can include:

Chronic illnesses or treatments (like chemotherapy) that affect the immune system;

Severe and life-threatening allergies to vaccine ingredients, which are very rare;

If you have severe illness and a high fever on the day of vaccination.

These factors often vary for each vaccine. If you’re not sure if you or your child should get a particular vaccine, talk to your health worker. They can help you make an informed choice about vaccination for you or your child.

All the ingredients of a vaccine play an important role in ensuring a vaccine is safe and effective. Some of these include:

The antigen. This is a killed or weakened form of a virus or bacteria, which trains our bodies to recognize and fight the disease if we encounter it in the future.

Adjuvants, which help to boost our immune response. This means they help vaccines to work better.

Preservatives, which ensure a vaccine stays effective.

Stabilisers, which protect the vaccine during storage and transportation.

Vaccine ingredients can look unfamiliar when they are listed on a label. However, many of the components used in vaccines occur naturally in the body, in the environment, and in the foods we eat. All of the ingredients in vaccines – as well as the vaccines themselves - are thoroughly tested and monitored to ensure they are safe.

Vaccination is safe and side effects from a vaccine are usually minor and temporary, such as a sore arm or mild fever. More serious side effects are possible, but extremely rare.

Any licensed vaccine is rigorously tested across multiple phases of trials before it is approved for use, and regularly reassessed once it is introduced. Scientists are also constantly monitoring information from several sources for any sign that a vaccine may cause health risks.

Remember, you are far more likely to be seriously injured by a vaccine-preventable disease than by a vaccine. For example, tetanus can cause extreme pain, muscle spasms (lockjaw) and blood clots, measles can cause encephalitis (an infection of the brain) and blindness. Many vaccine-preventable diseases can even result in death. The benefits of vaccination greatly outweigh the risks, and many more illnesses and deaths would occur without vaccines.

More information about vaccine safety and development is available here.

Like any medicine, vaccines can cause mild side effects, such as a low-grade fever, or pain or redness at the injection site. Mild reactions go away within a few days on their own.

Severe or long-lasting side effects are extremely rare. Vaccines are continually monitored for safety, to detect rare adverse events.

Scientific evidence shows that giving several vaccines at the same time has no negative effect. Children are exposed to several hundred foreign substances that trigger an immune response every day. The simple act of eating food introduces new germs into the body, and numerous bacteria live in the mouth and nose.

When a combined vaccination is possible (e.g. for diphtheria, pertussis and tetanus), this means fewer injections and reduces discomfort for the child. It also means that your child is getting the right vaccine at the right time, to avoid the risk of contracting a potentially deadly disease.

There is  no evidence  of any link between vaccines and autism or autistic disorders. This has been demonstrated in many studies, conducted across very large populations.

The 1998 study which raised concerns about a possible link between measles-mumps-rubella (MMR) vaccine and autism was later found to be seriously flawed and fraudulent. The paper was subsequently retracted by the journal that published it, and the doctor that published it lost his medical license. Unfortunately, its publication created fear that led to dropping immunization rates in some countries, and subsequent outbreaks of these diseases.

We must all ensure we are taking steps to share only credible, scientific information on vaccines, and the diseases they prevent.

Virtually all cervical cancer cases start with a sexually transmitted HPV infection. If given before exposure to the virus, vaccination offers the best protection against this disease. Following vaccination, reductions of up to 90% in HPV infections in teenage girls and young women have been demonstrated by studies conducted in Australia, Belgium, Germany, New Zealand, Sweden, the United Kingdom and the United States of America.

In studies, the HPV vaccine has been shown to be  safe and effective . WHO recommends that all girls aged 9–14 years receive 2 doses of the vaccine, alongside cervical cancer screening later in life.

If you have questions about vaccines be sure to talk to your healthcare worker. He or she can provide you with science-based advice about vaccination for you and your family, including the recommended vaccination schedule in your country.

When looking online for information about vaccines, be sure to consult only trustworthy sources. To help you find them, WHO has reviewed and ‘certified’ many websites across the world that provide only information based on reliable scientific evidence and independent reviews by leading technical experts. These websites are all members of the Vaccine Safety Net .

Vaccines and immunization

Vaccines explained

COVID-19 Vaccine Delivery Partnership

Related Q&A

Q&A on vaccine safety

Coronavirus disease (COVID-19): Vaccines

Coronavirus disease (COVID-19): COVID-19 Vaccine research and development

Coronavirus disease (COVID-19): COVID-19 Vaccine access and allocation

Jagannath Chatterjee

The eternal problem....

Childhood Illnesses – Road to Health

• Standard childhood illnesses, such as measles, mumps, and even whooping cough, may be of key benefit to a child's developing immune system and it may be inadvisable to suppress these illnesses with immunisations. – Dr Phillip Incao, MD
• Childhood illnesses are a standard feature of childhood because the young body needs them. - Rudolf Steiner, Austrian Scientist
• All acute inflammatory childhood illness--measles, mumps, rubella, chicken pox, scarlatina, or whooping cough--develops the cell-mediated immune system – the deeper immunity
• Childhood illnesses create immunity for life. Vaccines can push diseases to an age where it is dangerous.

Childhood Illnesses Can Prevent Serious Conditions Later in Life

• In early 1997, a team of British physicians writing in Science noted : "Childhood infections may, therefore,�paradoxically protect against asthma.“ These infections�have a purpose in building general immunity.
• Danish physician Tove Ronne in The Lancet in 1985:�"Measles virus infection in childhood can prevent disease in adult life." Among these, Dr. Ronne listed skin disease, immune dysfunctions, degenerative diseases of bone and cartilage, and certain cancers.
• Measles can cure eczema. Induced measles can cause cancer to reduce (remission). Having measles, mumps, rubella in early childhood can prevent against allergies, eczema, asthma , cardiovascular disease mortality and cancer. Polio virus used for cancer remission
• Association of measles and mumps with cardiovascular disease: The Japan Collaborative Cohort (JACC) study.

Kubota Y, et al. Atherosclerosis. 2015. http://www.ncbi.nlm.nih.gov/m/pubmed/26122188/

Childhood Illnesses Protect Against Cancer

• Albonico et al found that adults are significantly protected against non-breast cancers -- genital, prostate, gastrointestinal, skin, lung, ear-nose-throat, and others -- if they contracted measles (odds ratio, OR = 0.45), rubella (OR = 0.38) or chickenpox (OR = 0.62) earlier in life. [ Med Hypotheses 1998; 51(4): 315-20].
• Montella et al found that contracting measles in childhood reduces the risk of developing lymphatic cancer in adulthood [ Leuk Res 2006; 30(8): 917-22].
• Alexander et al found that infection with measles during childhood is significantly protective -- it cuts the risk in half -- against developing Hodgkin's disease (OR = 0.53) [ Br J Cancer 2000; 82(5): 1117-21].
• Glaser et al also found that lymph cancer is significantly more likely in adults who were not infected with measles, mumps or rubella in childhood [ In J Cancer 2005; 115(4): 599-605].
• Gilham et al found that infants with the least exposure to common infections have the greatest risk of developing childhood leukemia [ BMJ 2005; 330: 1294].
• Urayama et al also found that early exposure to infections is protective against leukemia [ Int J Cancer 2011; 128(7): 1632-43].
• In the world of science, it is quite well known that having infections in early life protects against various cancers in later life

Disease Mortality Declined Before Vaccines Introduced – Australian Data . Data from USA, UK, New Zealand & Canada also reflect the same.

Disease Mortality Decline In US (1900-1980) Due to Better Living Conditions, Sanitation, Medical care – JAMA 1999. Vaccines not mentioned. 30 diseases studied. No widespread vaccinations in that period.

US – Major diseases

USA – Diphtheria, Measles

UK & France

Safety of Vaccines Questioned

• A steep rise in cases of Autism (moderate to very severe and mostly permanent disability in children) after more vaccines introduced in 1990’s raised questions over vaccine safety. Parents could know deterioration in children after receiving vaccine shots.
• Doubts raised over use of mercury in vaccines (Thiomersal) and links to Autism. Mercury contamination had led to similar symptoms in Japan and Iraq.
• It became known that Aluminum, Formalin, Polysorbate 80, Phenol, MSG, Neomycin, Squalene, human and animal matter was contained in vaccines.
• More and more parents started reporting vaccination injury and Autism (a severe disorder) after vaccines.

Vaccine Ingredients – a secret well kept

Vaccines and Autism

• Vehemently denied, yet link impossible to hide
• CDC studies trying to disprove link have run into controversies for hiding the link. Scandals during reign of Julie Gerberding
• Scientists openly discussed vaccine autism link – and more dangers – at Simpsonwood (2000) while trying to hide autism link in CDC studies but minutes of meeting were exposed
• Two CDC studies called Verstraeten studies showed very high vaccine autism link. One study was manipulated to show no link and published. The other showing considerable link still lies unpublished
• Another group of CDC studies called Danish studies came crashing down after its Principal Coordinator Dr Poul Thorsen was figured in most wanted list of US Police for having misappropriated the research funds
• Recently the De-Stefano study of CDC came under a storm as its co-author Dr William Thompson revealed data manipulation to hide huge vaccine autism link (340%). Scientists tried to destroy data in 2002.
• CDC now faces Congress investigation. It’s research division “paralyzed with fear”. Congressman Bill Posey submitted on 29 th July 2015

How do vaccines cause Autism?

• As per original CDC study findings, mercury in vaccines is responsible for causing Autism in children. Studies have now shown that mercury even in trace amounts can be responsible
• Independent researchers have also pointed out the clear causative role played by Aluminum present in vaccines
• As per award winning journalist Janine Roberts, the aluminum in vaccines is in form of nano particles so that vaccine ingredients can permeate each cell of the body. Obviously this has a devastating impact on the body.
• Both mercury and aluminum have the ability to cross both blood brain barrier as well as placenta barrier. Thus vaccines given to pregnant women can kick start autism in the infants
• Researchers have also pointed out that the use of animal and human matter in vaccines can cause severe autoimmune reactions and lead to autism
• Vaccines like DPT, DTaP, MMR, Chicken Pox, Hep-B are implicated. Graphs show increase in autism after these vaccines were introduced

Japan – MMR Vac & Autism

Japan – Autism drops as MMR temporarily suspended 1993

AAP Fellow Quits in Protest....

How are vaccines tested for safety?

• Vaccines are tested by manufacturers or persons or agencies under their control. No other agency usually tests them. Phase I to Phase III. Phase IV after release.
• Vaccines are tested on extremely healthy subjects for a very short time (7 to 14) days or till the time adverse events start appearing
• Often serious adverse events are explained away or not reported
• Vaccines are not tested against any genuine placebo. They are tested against the same vaccine without the antigen or some other equally toxic substance
• In India, the Supreme Court and even Parliament has questioned trials but vaccines continue.
• Official vaccinated vs un-vaccinated study never conducted

Vaccines can NEVER be safe for children!

What tests are needed?

• Tests by independent agencies lacking conflict of interest
• Testing against genuine inert placebo and not another vaccine or toxic substance.
• Multiple vaccines given at one visit; never tested!
• Effects of entire vaccine schedule never studied!
• Long term effects never studied! Never studied for causing cancer, infertility, admitted in literature!
• No official studies of vaccinated vs non vaccinated
• Studies required on three generations of mice. Research shows toxicity carried down across generations through breast milk, sperm, epigenetic change
• What is the impact on the human gene? Has it been already altered by vaccines?

1967 study – Trauma of vaccination

Epigenetic Study - 2013

2008: Genes Activated

Independent Vaccinated Vs Non Vaccinated

UK Data – Vaccine Reactions

Adverse reactions – US Data (published MedAlert)

Adverse effects Encountered (MedAlert)

USA, for the year 2013

HPV Vaccines: Deaths now 232 (June 2015)

HPV Vaccine – Reactions Reported

Baby Ian – Allergic Reaction to Hep-B Vaccine

Mercury in Vaccines – Reduced in Developed Nations

• Thiomersal (mercury compound) used in vaccines since 1930. Never tested by FDA. One human study on 21 meningitis patients (1929); all died in short period, attributed to meningitis.
• "As it turns out, we are injecting our children with 400 times the amount of mercury that FDA or EPA considers safe.” - Robert F. Kennedy, Jr. on vaccine-autism-mercury link, 6/22/05
• In June 22, 2000 FDA formally declared that mercury should be removed from vaccines in USA. However mercury still remains as trace amount. Some vaccines still contain mercury in high amounts
• In India and other developing countries full dose mercury remains in all non live virus vaccines �

Mercury – Neurotoxin & Genotoxin

• Mercury -second most poisonous element (second only to uranium). Brain neurons rapidly and permanently disintegrate in the presence of mercury within 30 minutes of exposure. Mercury is known to change a body’s chromosomes. Used as decontaminant in vaccines. Can cross blood brain and placenta barrier
• “Symptoms of high exposure to this class of mercury based compounds include: long term neurological disorders, liver disorders, injuries to the cardiovascular system and hematopoietic system, deafness and ataxia, death.” As genotoxin, mercury is more dangerous in smaller doses.
• Acute poisoning may cause gastrointestinal irritation and renal failure, coordination problems, tremors, mental disorders among many others. Mercury vapour can cause damage.
• Causes Autism as per CDC unpublished study (Relative Risk – 7.6!)

Rat Study – Thiomersal (Mercury Compound in vaccines)

Folia Neuropathol.  2010;48(4):258-69.

Lasting neuropathological changes in rat brain after intermittent neonatal administration of thimerosal.

Olczak M 1 ,  Duszczyk M ,  Mierzejewski P ,  Wierzba-Bobrowicz T ,  Majewska MD .

Thimerosal, an organomercurial added as a preservative to some vaccines, is a suspected iatrogenic factor, possibly contributing to paediatric neurodevelopmental disorders including autism . We examined the effects of early postnatal administration of thimerosal (four i.m. injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and 15) on brain pathology in Wistar rats. Numerous neuropathological changes were observed in young adult rats which were treated postnatally with thimerosal. They included: ischaemic degeneration of neurons and "dark" neurons in the prefrontal and temporal cortex, the hippocampus and the cerebellum, pathological changes of the blood vessels in the temporal cortex, diminished synaptophysin reaction in the hippocampus, atrophy of astroglia in the hippocampus and cerebellum, and positive caspase-3 reaction in Bergmann astroglia. These findings document neurotoxic effects of thimerosal, at doses equivalent to those used in infant vaccines or higher, in developing rat brain, suggesting likely involvement of this mercurial in neurodevelopmental disorders.

PMID: 21225508 [PubMed - indexed for MEDLINE]

• http://www.ncbi.nlm.nih.gov/pubmed/21225508

“Since excessive accumulation of extracellular glutamate is linked with excitotoxicity, our data imply that neonatal exposure to thimerosal-containing vaccines might induce excitotoxic brain injuries, leading to neurodevelopmental disorders..” – Quoted in subsequent study. (2012) http://www.ncbi.nlm.nih.gov/pubmed/22015977

Thiomersal Bottle – Notice the skull & bones warning

In the USA incidence of autism started to dip as mercury in vaccines were reduced by Order but the flu vaccine with mercury was introduced, and aluminum uptake increased in other vaccines

Aluminum – Cause of brain damage

• Aluminum is a suspected carcinogen. It is a cardiovascular or blood toxicant, neurotoxicant, and respiratory toxicant. It has been implicated as a cause of brain damage, and is a suspected factor in Alzheimer’s Disease, dementia, convulsions, and comas. Aluminum can cross the blood brain barrier .
• It suffers synergistic toxicity with mercury and can increase the toxicity of mercury 100 times. Aluminum and mercury are both present in vaccines.
• In humans, there have been reports of a chronic inflammation syndrome called macrophagic myofascitis (MMF) being induced by alum-based vaccines. Symptoms included myalgias, arthralgias, marked asthenia, muscle weakness, and fever. In cats, this vaccine ingredient causes cancers.�

Aluminum in Vaccines & Autism

Formaldehyde - Carcinogen

• Formaldehyde (Formalin in vaccines) is ranked as one of the most hazardous compounds on ecosystems and human health - Environmental Defense Fund. These findings are for environmental exposure, and therefore, the dangers are much greater for the formaldehyde included in vaccines, since it is injected directly into the blood (should not be). Declared carcinogen-Twelfth Report on Carcinogens (2011).
• Toxic symptoms are more than a hundred. Can cause cancer, asthma, eczema, attention and memory problems, damage to reproductive organs, jaundice, kidney pain, menstrual irregularities, schizophrenia like symptoms, sterility, blood vomiting etc
• Formaldehyde, when present with mercury and aluminum, increases toxicity of mercury 1000 times .

Beats logic..

Package Insert - MMR

Package Insert – Hep B Vaccine

Package Insert – Chicken Pox Vaccine

Some other issues with vaccines

• According to medical texts, infants should not be given anything else except breast milk; not even water. Then how do they allow the extremely toxic vaccine injections? – Dr Suzanne Humphries
• Vaccinated mothers no longer have natural antibodies that they can pass on to children via breast milk. Therefore infants have become more vulnerable creating a vicious cycle
• Vaccines are an industrial product, manufactured for profits. Vaccine markets are created to generate more revenue. Effects on children are overlooked.
• Vaccines are now being mandated in the USA and Australia. This is in gross violation of parental rights and also of the Nuremburg Code and AMA’s own guidelines. The Senators pushing these mandates were exposed,paid by pharma as part of their lobbying
• The CDC of USA which recommends vaccines has a for-profit wing which receives generous funds from vaccine industry. Even WHO depends on industry funding. They cannot be trusted.

Are vaccines effective?

• Vaccines are supposed to produce humoral (blood related antibodies) that theoretically protect us against infections? Is this theory correct?
• It is known that, in many instances, antigen-specific antibody titers do not correlate with protection. In addition, very little is known on parameters of cell-mediated immunity which could be considered as surrogates of protection. (Del Giudice G et al, 2001)
• In a study published in Neurology it was demonstrated that titers (the measurement of the levels of antibodies in the bloodstream) were poor indicators of immunity. (Nathan E Crone et al, 1992)
• A titer test does not and cannot measure immunity, because immunity to specific viruses is reliant not on antibodies, but on memory cells – Expert testimony before European Court of Human Rights, 2006

Vaccine Failures!

• Diseases vaccinations are supposed to prevent regularly occur in fully vaccinated populations.
• A measles outbreak in early 1989 among approximately 4200 vaccinated students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure. (Pubmed)
• Mumps Outbreaks in Vaccinated Populations: Are Available Mumps Vaccines Effective Enough to Prevent Outbreaks? (Pubmed)
• Disease outbreaks are concentrated in highest-vaccinated population – Council on Foreign Relations Graph
• Whooping cough outbreaks are HIGHER among vaccinated children compared with unvaccinated children- Dr. David Witt, infectious disease specialist at the Kaiser Permanente Medical Center in California.
• In India measles vaccine is failing to prevent measles - Report �

Vaccines increase susceptibility!

• Vaccinated individuals are often made more susceptible to the diseases they are vaccinated against and are more likely to die from it.
• Dr R P Garrow reports in the British Medical Journal, Jan 14, 1928, that a person vaccinated against Small Pox was five times more likely to die of the disease than the unvaccinated.
• He also reported, the vaccination was causing a great surge in cases of Small Pox in areas where it was widely given
• Using RTI data doctors in India reported that children given the Oral Polio Vaccine are 6.26 times more likely to suffer paralysis than the unvaccinated.
• Measles after vaccination is more deadly.

Vaccines Cause Serious Side Effects

• The DaPT vaccine Tripedia has listed Autism and ADHD as a side effect. The DPT vaccine is linked to asthma, provocative polio, hyperactivity and learning disorders in children. A 1948 study by Dr Byers et al linked it to deaths, blindness, deafness, spasticity, convulsions, and other severe neurological disorders.
• The Hepatitis B vaccine has been linked to serious adverse effects including cancer of liver. Combination vaccines have more adverse effects; MMR, DPT, Pentavalent etc
• Vaccines are known to cause- Allergies * Asthma * Attention Deficit Disorder *Autism * Auto-immune Diseases * Blindness * Brain Cell Loss *Cancer * Central Nervous System Damage* Deafness * Developmental Damage *DEATH * Diabetes * Epilepsy * Learning Disabilities * Leukemia * Multiple Sclerosis * Neurological Disease * Organ Disease * Psoriasis * Seizures * Shaken Baby Syndrome * SIDS * Total Paralysis * All Diseases in Internal Medicine
• All vaccines can do harm – Dr Andrew Moulden, MD. Vaccines can never be safe – Dr Suzanne Humphries, MD

200 adverse effects compiled from published research papers � http://www.greenmedinfo.com/blog/200-evidence-based-reasons-not-vaccinate-free-research-pdf-download

Vaccine victims are mocked..

Vaccines being opposed by Dr’s and Medical Scientists in India

• BCG – Tested in 15 year trial in India. 0% effective!
• Hep-B vaccine – Meant for promiscuous adults in developed nations, now given to children in developing countries because they refused
• Oral Polio Vaccine – Known to cause polio; both individual cases and epidemics. Court case filed (CCF).
• Pentavalent vaccine – Very high death rate & hospitalization in all countries introduced. CCF
• HPV vaccine – Trial in India conducted unethically killing 7 (9?) tribal adolescent girls. Supreme Court
• Rota Vaccine – Rota diarrhea can be controlled by ORS. The vaccine has serious adverse effect. Recent Indian vaccine to be launched hiding trial data. CCF

How vaccines ‘eradicate disease’

• Disease rates are inflated 100 to 1000 times before vaccines are introduced
• Disease definition is changed when vaccines are introduced making it difficult to report the disease
• Doctors are advised that, ‘vaccinated children cannot come down with the disease vaccinated against’. So they change disease names when such cases come up
• Symptoms (for the same disease) are bifurcated to create new disease names and show drop in cases
• Pathology samples can be checked in only pre-selected laboratories so that positive cases can be suppressed
• Low level health workers or officials cannot report disease, they have to go through ‘experts’ who can then suppress cases

How Polio Was “Eradicated”

• 32,419 cases of the disease were inflated to 3,50,000. In India the figure was 12,000
• Definition of polio was changed three times to bring down number of cases
• A disease name called “Non Polio Acute Flaccid Paralysis” was created to bifurcate polio figures. Polio is traditionally infantile paralysis. It was changed to viral polio. Earlier 20 days duration was required to identify polio, it was increased to 60 days.
• Pathological tests could be carried out only in select WHO certified laboratories
• Cases of polio caused due the vaccine were suppressed
• Paralysis in children increased from 1005 in 1996 to 60,992 in 2012 after India was declared polio free!

Polio Vac – Controversial since 1955!

Oral Polio Vac and Cancer!

Polio Incidence & Pesticide (DDT)

Change in Polio Definition

• Traditionally infantile paralysis of any kind lasting more than 24 hours was recorded as polio
• After vaccine introduced only polio caused by 3 enteroviruses were considered polio. Other paralysis was given different names
• Later paralysis had to last more than 20 days
• This was increased to 60 days
• In addition, stools had to confirm presence of PV
• Only WHO accredited laboratories can confirm
• Polio caused by vaccine or vaccine strain virus turned virulent cannot be called polio
• Polio recorded as “Non Polio Acute Flaccid Paralysis”
• “Clinically indistinguishable and twice as deadly” –Dr’s

Polio – Controlled by vaccine?

You think Small Pox Was Eradicated by Vaccines?

• The practice of inoculation (against small pox) manifestly tends to spread the contagion, for a contagious disease is produced by innoculation where it would not otherwise have produced. The Gentleman’s Magazine and Historical Chronicle, vol.34, 1764,p.333
• In the 38 years after the start of innoculation, deaths from small pox relative to the number born increased to 127 per 1,000 (a 41 % increase) and relative to the number of burials (deaths) 81 per 1,000 (a 27% increase). The Great Small Pox Epidemic of 1775-82, History Today, July 20, 2003, p.12
• Since the late 1700s, the medical profession has supported vaccination without comparing vaccinated and unvaccinated. MMWR, vol.50, CDC, June 22, 2001, pp1-25
• ...the level of antibody that protects against small pox is unknown. ibid

Why did Gandhi revolt against vaccines?

• Gandhiji revolted against vaccines and declared it a ‘filthy process’. Why?
• “When we recall that vaccine lymph is derived, in the first place, either from a small pox corpse, the ulcerated udder of a cow, or the running sores of a sick horse’s heels...it has far reaching ill effects on the human constitution”. Studies in Vaccinia, The Lancet, vol. 1999, no.5150, May 13, 1922
• No practitioner knows whether the lymph he employs is derived from small pox, rabbit pox, ass-pox or mule pox. Ibid. (What viruses were in the vaccines? Even CDC does not know! Admitted after genetic assay of Dryvax)
• Some of the animals that have been used to passage today’s vaccine virus include rabbits, mice, goats, cows, pigs, horses, sheep, dogs, birds and humans.�

Small Pox Vaccine & Cancer

What else did the vaccine cause?

• “In these cases it is highly likely that acute infectious hepatitis was a result of contamination of human lymph derived vaccine. Other infectious diseases attributed to vaccination includes tuberculosis & syphillis” New York Times, Sept 26, 1869
• In the year 1981, a WHO consultant released to the media, that his investigation into the AIDS epidemic under the instruction of WHO, clearly revealed that HIV spread to humans from primates due to the small pox vaccine. WHO suppressed the report.
• The vaccine was linked to eczema vaccinatum with a fatality rate of 4-40%. Also linked to erisypelus epidemics which had high mortality rates. CNS damage.
• Huge epidemics of small pox in 1872-73 (Boston) started AFTER introduction of vaccine.

Leicester Small Pox Spike After Mandatory Vaccination. This UK state eliminated small pox with isolation, sanitation and nutrition

Testimonial of a Nobel Prize Winner

Blind Belief in Doctors – Not Recommended!

Educate before you vaccinate!

• Neither government or doctors will inform you about vaccine dangers
• If your child dies, becomes disabled or diseased it will be denied by authorities and marked ‘coincidence’
• You will not receive any free treatment, compensation or any rehabilitation help for your child
• The very doctor who vaccinated your child will become your enemy
• Doctors receive commissions, political parties receive funds, bureaucrats receive perks and promotions. You gain a dead, sick or disabled child!
• As per a law signed into effect in the USA in 1986 vaccine manufacturers and even individual vaccines are protected from law suits
• Vaccine industry & doctors protected, not your child!

Profitable industrial product

To Protect Your Child

• Ensure adequate age for marriage
• Provide proper nutrition and care for pregnant mother
• Homeopathic treatment during pregnancy will ensure a healthy child. Search for senior homeopath.
• Avoid drugs and vaccines during pregnancy. The tetanus vaccine being given during pregnancy is also used to sterilize girls and women in developing nations (used in India, Kenya). It can cause abortions and premature birth.
• Go in for natural child birth. Delay cord clamping. Do not clean child immediately after birth. Learn from natural birth movement. Aisharwaya Rai Bachhan did this!
• Give the first yellow milk – colostrum- to your child. You can breastfeed up to 2 years & beyond for benefits and emotional bonding
• Give baby homeopathic treatment during illnesses

What do other systems recommend?

• Ayurveds flay village practice of giving even a drop of honey to infants
• Homeopathic texts talk about giving medicines to mothers so that children get it through breast milk
• Pregnancy, infancy and childhood are to be respected
• General practitioners (GP’s) were wary about medicating these groups. Vaccination was selective based upon child’s health. Many also conducted skin tests before administration. Seniors were more cautious and even skipped them if they perceived no threat
• Things changed after paediatricians arrived on the scene. They are reckless about vaccination and prescribing antibiotics etc for resultant conditions

Role of civil society

• Medicine is too important to be left at the hands of doctors. Civil society should not forget its watchdog role
• Civil society representatives should be a part of the National Technical Advisory Group on Immunizations that advises GoI on vaccinations
• The civil society should sensitize doctors on vaccine dangers. The industry keeps them in the dark
• Awareness about the murky world of vaccines ought to be created among the general populations
• Should demand a vaccine adverse event reporting system with compulsory reporting and monitor the same and seek compensation and rehabilitation for victims
• Vaccines crimes need to be referred to civil and criminal courts. Protecting vaccines is the goal of medical boards.

Be scientific...

Vaccine Information Websites

• www.nvic.org
• www.sanevax.org
• www.mercola.com
• www.greenmedinfo.com
• www.vaccineresearchlibrary.com
• www.vactruth.com
• www.vaccinetruth.org
• www.currenthealthscenario.blogspot.in
• www.vaccinationinformationnetwork.org
• www.naturalnews.com

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• Review Article
• Published: 22 December 2020

A guide to vaccinology: from basic principles to new developments

• Andrew J. Pollard   ORCID: orcid.org/0000-0001-7361-719X 1 , 2 &
• Else M. Bijker 1 , 2  

Nature Reviews Immunology volume  21 ,  pages 83–100 ( 2021 ) Cite this article

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• Infectious diseases

A Publisher Correction to this article was published on 05 January 2021

This article has been updated

Immunization is a cornerstone of public health policy and is demonstrably highly cost-effective when used to protect child health. Although it could be argued that immunology has not thus far contributed much to vaccine development, in that most of the vaccines we use today were developed and tested empirically, it is clear that there are major challenges ahead to develop new vaccines for difficult-to-target pathogens, for which we urgently need a better understanding of protective immunity. Moreover, recognition of the huge potential and challenges for vaccines to control disease outbreaks and protect the older population, together with the availability of an array of new technologies, make it the perfect time for immunologists to be involved in designing the next generation of powerful immunogens. This Review provides an introductory overview of vaccines, immunization and related issues and thereby aims to inform a broad scientific audience about the underlying immunological concepts.

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Introduction.

Vaccines have transformed public health, particularly since national programmes for immunization first became properly established and coordinated in the 1960s. In countries with high vaccine programme coverage, many of the diseases that were previously responsible for the majority of childhood deaths have essentially disappeared 1 (Fig.  1 ). The World Health Organization (WHO) estimates that 2–3 million lives are saved each year by current immunization programmes, contributing to the marked reduction in mortality of children less than 5 years of age globally from 93 deaths per 1,000 live births in 1990 to 39 deaths per 1,000 live births in 2018 (ref. 2 ).

The introduction of vaccination against infectious diseases such as diphtheria (part a ), capsular group C meningococcus (part b ), polio (part c ), Haemophilus influenzae type B (part d ), measles (part e ) and pertussis (part f ) led to a marked decrease in their incidence. Of note, the increase in reports of H. influenzae type B in 2001 led to a catch-up vaccination campaign, after which the incidence reduced. For pertussis, a decline in vaccine coverage led to an increase in cases in the late 1970s and 1980s, but disease incidence reduced again after vaccine coverage increased. Adapted with permission from the Green Book, information for public health professionals on immunisation, Public Health England , contains public sector information licensed under the Open Government Licence v3.0.

Vaccines exploit the extraordinary ability of the highly evolved human immune system to respond to, and remember, encounters with pathogen antigens . However, for much of history, vaccines have been developed through empirical research without the involvement of immunologists. There is a great need today for improved understanding of the immunological basis for vaccination to develop vaccines for hard-to-target pathogens (such as Mycobacterium tuberculosis , the bacterium that causes tuberculosis (TB)) 3 and antigenically variable pathogens (such as HIV) 4 , to control outbreaks that threaten global health security (such as COVID-19 or Ebola) 5 , 6 and to work out how to revive immune responses in the ageing immune system 7 to protect the growing population of older adults from infectious diseases.

In this Review, which is primarily aimed at a broad scientific audience, we provide a guide to the history (Box  1 ), development, immunological basis and remarkable impact of vaccines and immunization programmes on infectious diseases to provide insight into the key issues facing immunologists today. We also provide some perspectives on current and future challenges in continuing to protect the world’s population from common pathogens and emerging infectious threats. Communicating effectively about the science of vaccination to a sceptical public is a challenge for all those engaged in vaccine immunobiology but is urgently needed to realign the dialogue and ensure public health 8 . This can only be achieved by being transparent about what we know and do not know, and by considering the strategies to overcome our existing knowledge gaps.

Box 1 A brief history of vaccination

Epidemics of smallpox swept across Europe in the seventeenth and eighteenth centuries, accounting for as much as 29% of the death rate of children in London 137 . Initial efforts to control the disease led to the practice of variolation, which was introduced to England by Lady Mary Wortley Montagu in 1722, having been used in the Far East since the mid-1500s (see Nature Milestones in Vaccines ). In variolation, material from the scabs of smallpox lesions was scratched into the skin in an attempt to provide protection against the disease. Variolation did seem to induce protection, reducing the attack rate during epidemics, but sadly some of those who were variolated developed the disease and sometimes even died. It was in this context that Edward Jenner wrote ‘An Inquiry into the Causes and Effects of the Variole Vaccinae…’ in 1798. His demonstration, undertaken by scratching material from cowpox lesions taken from the hands of a milkmaid, Sarah Nelms, into the skin of an 8-year-old boy, James Phipps, who he subsequently challenged with smallpox, provided early evidence that vaccination could work. Jenner’s contribution to medicine was thus not the technique of inoculation but his startling observation that milkmaids who had had mild cowpox infections did not contract smallpox, and the serendipitous assumption that material from cowpox lesions might immunize against smallpox. Furthermore, Jenner brilliantly predicted that vaccination could lead to the eradication of smallpox; in 1980, the World Health Assembly declared the world free of naturally occurring smallpox.

Almost 100 years after Jenner, the work of Louis Pasteur on rabies vaccine in the 1880s heralded the beginning of a frenetic period of development of new vaccines, so that by the middle of the twentieth century, vaccines for many different diseases (such as diphtheria, pertussis and typhoid) had been developed as inactivated pathogen products or toxoid vaccines. However, it was the coordination of immunization as a major public health tool from the 1950s onwards that led to the introduction of comprehensive vaccine programmes and their remarkable impact on child health that we enjoy today. In 1974, the World Health Organization launched the Expanded Programme on Immunization and a goal was set in 1977 to reach every child in the world with vaccines for diphtheria, pertussis, tetanus, poliomyelitis, measles and tuberculosis by 1990. Unfortunately, that goal has still not been reached; although global coverage of 3 doses of the diphtheria–tetanus–pertussis vaccine has risen to more than 85%, there are still more than 19 million children who did not receive basic vaccinations in 2019 (ref. 105 ).

What is in a vaccine?

A vaccine is a biological product that can be used to safely induce an immune response that confers protection against infection and/or disease on subsequent exposure to a pathogen. To achieve this, the vaccine must contain antigens that are either derived from the pathogen or produced synthetically to represent components of the pathogen. The essential component of most vaccines is one or more protein antigens that induce immune responses that provide protection. However, polysaccharide antigens can also induce protective immune responses and are the basis of vaccines that have been developed to prevent several bacterial infections, such as pneumonia and meningitis caused by Streptococcus pneumoniae , since the late 1980s 9 . Protection conferred by a vaccine is measured in clinical trials that relate immune responses to the vaccine antigen to clinical end points (such as prevention of infection, a reduction in disease severity or a decreased rate of hospitalization). Finding an immune response that correlates with protection can accelerate the development of and access to new vaccines 10 (Box  2 ).

Vaccines are generally classified as live or non-live (sometimes loosely referred to as ‘inactivated’) to distinguish those vaccines that contain attenuated replicating strains of the relevant pathogenic organism from those that contain only components of a pathogen or killed whole organisms (Fig.  2 ). In addition to the ‘traditional’ live and non-live vaccines, several other platforms have been developed over the past few decades, including viral vectors, nucleic acid-based RNA and DNA vaccines, and virus-like particles (discussed in more detail later).

Schematic representation of different types of vaccine against pathogens; the text indicates against which pathogens certain vaccines are licensed and when each type of vaccine was first introduced. BCG, Mycobacterium bovis bacillus Calmette–Guérin.

The distinction between live and non-live vaccines is important. The former may have the potential to replicate in an uncontrolled manner in immunocompromised individuals (for example, children with some primary immunodeficiencies, or individuals with HIV infection or those receiving immunosuppressive drugs), leading to some restrictions to their use 11 . By contrast, non-live vaccines pose no risk to immunocompromised individuals (although they may not confer protection in those with B cell or combined immunodeficiency, as explained in more detail later).

Live vaccines are developed so that, in an immunocompetent host, they replicate sufficiently to produce a strong immune response, but not so much as to cause significant disease manifestations (for example, the vaccines for measles, mumps, rubella and rotavirus, oral polio vaccine, the Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccine for TB and live attenuated influenza vaccine). There is a trade-off between enough replication of the vaccine pathogen to induce a strong immune response and sufficient attenuation of the pathogen to avoid symptomatic disease. For this reason, some safe, live attenuated vaccines require multiple doses and induce relatively short-lived immunity (for example, the live attenuated typhoid vaccine, Ty21a) 12 , and other live attenuated vaccines may induce some mild disease (for example, about 5% of children will develop a rash and up to 15% fever after measles vaccination) 13 .

The antigenic component of non-live vaccines can be killed whole organisms (for example, whole-cell pertussis vaccine and inactivated polio vaccine), purified proteins from the organism (for example, acellular pertussis vaccine), recombinant proteins (for example, hepatitis B virus (HBV) vaccine) or polysaccharides (for example, the pneumococcal vaccine against S. pneumoniae ) (Fig.  2 ). Toxoid vaccines (for example, for tetanus and diphtheria) are formaldehyde-inactivated protein toxins that have been purified from the pathogen.

Non-live vaccines are often combined with an adjuvant to improve their ability to induce an immune response (immunogenicity). There are only a few adjuvants that are used routinely in licensed vaccines. However, the portfolio of adjuvants is steadily expanding, with liposome-based adjuvants and oil-in-water emulsions being licensed in the past few decades 14 . The mechanism of action of aluminium salts (alum), although extensively used as an adjuvant for more than 80 years, remains incompletely understood 15 , but there is increasing evidence that immune responses and protection can be enhanced by the addition of newer adjuvants that provide danger signals to the innate immune system . Examples of these novel adjuvants are the oil-in-water emulsion MF59, which is used in some influenza vaccines 16 ; AS01 , which is used in one of the shingles vaccines and the licensed malaria vaccine 17 ; and AS04 , which is used in a vaccine against human papillomavirus (HPV) 18 .

Vaccines contain other components that function as preservatives, emulsifiers (such as polysorbate 80) or stabilizers (for example, gelatine or sorbitol). Various products used in the manufacture of vaccines could theoretically also be carried over to the final product and are included as potential trace components of a vaccine, including antibiotics, egg or yeast proteins, latex, formaldehyde and/or gluteraldehyde and acidity regulators (such as potassium or sodium salts). Except in the case of allergy to any of these components, there is no evidence of risk to human health from these trace components of some vaccines 19 , 20 .

Box 2 Correlates of protection

The identification of correlates of protection is helpful in vaccine development as they can be used to compare products and to predict whether the use of an efficacious vaccine in a new population (for example, a different age group, medical background or geographical location) is likely to provide the same protection as that observed in the original setting. There is considerable confusion in the literature about the definition of a correlate of protection. For the purposes of this discussion, it is useful to separate out two distinct meanings. A mechanistic correlate of protection is the specific functional immune mechanism that is believed to confer protection. For example, antitoxin antibodies, which are induced by the tetanus toxoid vaccine, confer protection directly by neutralizing the activity of the toxin. A non-mechanistic correlate of protection does not in itself provide the protective function but has a statistical relationship with the mechanism of protection. An example of a non-mechanistic correlate of protection is total IgG antibody levels against pneumococci. These IgG antibodies contain the mechanistic correlate (thought to be a subset of opsonophagocytic antibodies ) but the mechanism of protection is not being directly measured. Correlates of protection can be measured in clinical trials if there are post-vaccination sera available from individuals who do or do not develop disease, although large-scale serum collection from participants is rarely undertaken in phase III clinical efficacy trials. An alternative approach is to estimate the correlates of protection by extrapolating from sero-epidemiological studies in a vaccinated population and relating the data to disease incidence in the population. Human challenge studies have also been used to determine correlates of protection, although the dose of challenge bacterium or virus and the experimental conditions may not relate closely to natural infection, which can limit the utility of these observations.

Vaccines induce antibodies

The adaptive immune response is mediated by B cells that produce antibodies (humoral immunity) and by T cells (cellular immunity). All vaccines in routine use, except BCG (which is believed to induce T cell responses that prevent severe disease and innate immune responses that may inhibit infection; see later), are thought to mainly confer protection through the induction of antibodies (Fig.  3 ). There is considerable supportive evidence that various types of functional antibody are important in vaccine-induced protection, and this evidence comes from three main sources: immunodeficiency states, studies of passive protection and immunological data.

The immune response following immunization with a conventional protein antigen. The vaccine is injected into muscle and the protein antigen is taken up by dendritic cells, which are activated through pattern recognition receptors (PRRs) by danger signals in the adjuvant, and then trafficked to the draining lymph node. Here, the presentation of peptides of the vaccine protein antigen by MHC molecules on the dendritic cell activates T cells through their T cell receptor (TCR). In combination with signalling (by soluble antigen) through the B cell receptor (BCR), the T cells drive B cell development in the lymph node. Here, the T cell-dependent B cell development results in maturation of the antibody response to increase antibody affinity and induce different antibody isotypes. The production of short-lived plasma cells, which actively secrete antibodies specific for the vaccine protein, produces a rapid rise in serum antibody levels over the next 2 weeks. Memory B cells are also produced, which mediate immune memory. Long-lived plasma cells that can continue to produce antibodies for decades travel to reside in bone marrow niches. CD8 + memory T cells can proliferate rapidly when they encounter a pathogen, and CD8 + effector T cells are important for the elimination of infected cells.

Immunodeficiency states

Individuals with some known immunological defects in antibodies or associated immune components are particularly susceptible to infection with certain pathogens, which can provide insight into the characteristics of the antibodies that are required for protection from that particular pathogen. For example, individuals with deficiencies in the complement system are particularly susceptible to meningococcal disease caused by infection with Neisseria meningitidis 21 because control of this infection depends on complement-mediated killing of bacteria, whereby complement is directed to the bacterial surface by IgG antibodies. Pneumococcal disease is particularly common in individuals with reduced splenic function 22 (which may be congenital, resulting from trauma or associated with conditions such as sickle cell disease); S. pneumoniae bacteria that have been opsonized with antibody and complement are normally removed from the blood by phagocytes in the spleen, which are no longer present in individuals with hyposplenism. Antibody-deficient individuals are susceptible to varicella zoster virus (which causes chickenpox) and other viral infections, but, once infected, they can control the disease in the same way as an immunocompetent individual, so long as they have a normal T cell response 23 .

Passive protection

It has been clearly established that intramuscular or intravenous infusion of exogenous antibodies can provide protection against some infections. The most obvious example is that of passive transfer of maternal antibodies across the placenta, which provides newborn infants with protection against a wide variety of pathogens, at least for a few months after birth. Maternal vaccination with pertussis 24 , tetanus 25 and influenza 26 vaccines harnesses this important protective adaptation to reduce the risk of disease soon after birth and clearly demonstrates the role of antibodies in protection against these diseases. Vaccination of pregnant women against group B streptococci 27 and respiratory syncytial virus (RSV) 28 has not yet been shown to be effective at preventing neonatal or infant infection, but it has the potential to reduce the burden of disease in the youngest infants. Other examples include the use of specific neutralizing antibodies purified from immune donors to prevent the transmission of various viruses, including varicella zoster virus, HBV and measles virus 29 . Individuals with inherited antibody deficiency are without defence against serious viral and bacterial infections, but regular administration of serum antibodies from an immunocompetent donor can provide almost entirely normal immune protection for the antibody-deficient individual.

Immunological data

Increasing knowledge of immunology provides insights into the mechanisms of protection mediated by vaccines. For example, polysaccharide vaccines, which are made from the surface polysaccharides of invasive bacteria such as meningococci ( N. meningitidis ) 30 and pneumococci ( S. pneumoniae ) 31 , provide considerable protection against these diseases. It is now known that these vaccines do not induce T cell responses, as polysaccharides are T cell-independent antigens , and thus they must mediate their protection through antibody-dependent mechanisms. Protein–polysaccharide conjugate vaccines contain the same polysaccharides from the bacterial surface, but in this case they are chemically conjugated to a protein carrier (mostly tetanus toxoid, or diphtheria toxoid or a mutant protein derived from it, known as CRM 197 ) 32 , 33 , 34 . The T cells induced by the vaccine recognize the protein carrier (a T cell-dependent antigen ) and these T cells provide help to the B cells that recognize the polysaccharide, but no T cells are induced that recognize the polysaccharide and, thus, only antibody is involved in the excellent protection induced by these vaccines 35 . Furthermore, human challenge studies offer the opportunity to efficiently assess correlates of protection (Box  2 ) under controlled circumstances 36 , and they have been used to demonstrate the role of antibodies in protection against malaria 37 and typhoid 38 .

Vaccines need T cell help

Although most of the evidence points to antibodies being the key mediators of sterilizing immunity induced by vaccination, most vaccines also induce T cell responses. The role of T cells in protection is poorly characterized, except for their role in providing help for B cell development and antibody production in lymph nodes. From studies of individuals with inherited or acquired immunodeficiency, it is clear that whereas antibody deficiency increases susceptibility to acquisition of infection, T cell deficiency results in failure to control a pathogen after infection. For example, T cell deficiency results in uncontrolled and fatal varicella zoster virus infection, whereas individuals with antibody deficiency readily develop infection but recover in the same way as immunocompetent individuals. The relative suppression of T cell responses that occurs at the end of pregnancy increases the severity of infection with influenza and varicella zoster viruses 39 .

Although evidence for the involvement of T cells in vaccine-induced protection is limited, this is likely owing, in part, to difficulties in accessing T cells to study as only the blood is easily accessible, whereas many T cells are resident in tissues such as lymph nodes. Furthermore, we do not yet fully understand which types of T cell should be measured. Traditionally, T cells have been categorized as either cytotoxic (killer) T cells or helper T cells. Subtypes of T helper cells (T H cells) can be distinguished by their profiles of cytokine production. T helper 1 (T H 1) cells and T H 2 cells are mainly important for establishing cellular immunity and humoral immunity, respectively, although T H 1 cells are also associated with generation of the IgG antibody subclasses IgG1 and IgG3. Other T H cell subtypes include T H 17 cells (which are important for immunity at mucosal surfaces such as the gut and lung) and T follicular helper cells (located in secondary lymphoid organs, which are important for the generation of high-affinity antibodies (Fig.  3 )). Studies show that sterilizing immunity against carriage of S. pneumoniae in mice can be achieved by the transfer of T cells from donor mice exposed to S. pneumoniae 40 , which indicates that further investigation of T cell-mediated immunity is warranted to better understand the nature of T cell responses that could be harnessed to improve protective immunity.

Although somewhat simplistic, the evidence therefore indicates that antibodies have the major role in prevention of infection (supported by T H cells), whereas cytotoxic T cells are required to control and clear established infection.

Features of vaccine-induced protection

Vaccines have been developed over the past two centuries to provide direct protection of the immunized individual through the B cell-dependent and T cell-dependent mechanisms described above. As our immunological understanding of vaccines has developed, it has become apparent that this protection is largely manifested through the production of antibody. Another important feature of vaccine-induced protection is the induction of immune memory . Vaccines are usually developed to prevent clinical manifestations of infection. However, some vaccines, in addition to preventing the disease, may also protect against asymptomatic infection or colonization, thereby reducing the acquisition of a pathogen and thus its onward transmission, establishing herd immunity. Indeed, the induction of herd immunity is perhaps the most important characteristic of immunization programmes, with each dose of vaccine protecting many more individuals than the vaccine recipient. Some vaccines may also drive changes in responsiveness to future infections with different pathogens, so called non-specific effects, perhaps by stimulating prolonged changes in the activation state of the innate immune system.

Immune memory

In encountering a pathogen, the immune system of an individual who has been vaccinated against that specific pathogen is able to more rapidly and more robustly mount a protective immune response. Immune memory has been shown to be sufficient for protection against pathogens when the incubation period is long enough for a new immune response to develop (Fig.  4a ). For example, in the case of HBV, which has an incubation period of 6 weeks to 6 months, a vaccinated individual is usually protected following vaccination even if exposure to the virus occurs some time after vaccination and the levels of vaccine-induced antibody have already waned 41 . Conversely, it is thought that immune memory may not be sufficient for protection against rapidly invasive bacterial infections that can cause severe disease within hours or days following acquisition of the pathogen 42 (Fig.  4b ). For example, there is evidence in the case of both Haemophilus influenzae type B (Hib) and capsular group C meningococcal infection that individuals with vaccine-induced immune memory can still develop disease once their antibody levels have waned, despite mounting robust, although not rapid enough, memory responses 43 , 44 . The waning of antibody levels varies depending on the age of the vaccine recipient (being very rapid in infants as a result of the lack of bone marrow niches for B cell survival), the nature of the antigen and the number of booster doses administered. For example, the virus-like particles used in the HPV vaccine induce antibody responses that can persist for decades, whereas relatively short-term antibody responses are induced by pertussis vaccines; and the inactivated measles vaccine induces shorter-lived antibody responses than the live attenuated measles vaccine.

Antibody levels in the circulation wane after primary vaccination, often to a level below that required for protection. Whether immune memory can protect against a future pathogen encounter depends on the incubation time of the infection, the quality of the memory response and the level of antibodies induced by memory B cells. a | The memory response may be sufficient to protect against disease if there is a long incubation period between pathogen exposure and the onset of symptoms to allow for the 3–4 days required for memory B cells to generate antibody titres above the protective threshold. b | The memory response may not be sufficient to protect against disease if the pathogen has a short incubation period and there is rapid onset of symptoms before antibody levels have reached the protective threshold. c | In some cases, antibody levels after primary vaccination remain above the protective threshold and can provide lifelong immunity.

So, for infections that are manifest soon after acquisition of the pathogen, the memory response may be insufficient to control these infections and sustained immunity for individual protection through vaccination can be difficult to achieve. One solution to this is the provision of booster doses of vaccine through childhood (as is the case, for example, for diphtheria, tetanus, pertussis and polio vaccines), in an attempt to sustain antibody levels above the protective threshold. It is known that provision of five or six doses of tetanus 45 or diphtheria 46 vaccine in childhood provides lifelong protection, and so booster doses of these vaccines throughout adult life are not routine in most countries that can achieve high coverage with multiple childhood doses. Given that, for some infections, the main burden is in young children, continued boosting after the second year of life is not undertaken (for example, the invasive bacterial infections including Hib and capsular group B meningococci).

The exception is the pertussis vaccine, where the focus of vaccine programmes is the prevention of disease in infancy; this is achieved both by direct vaccination of infants as well as by the vaccination of other age groups, including adolescents and pregnant women in some programmes, to reduce transmission to infants and provide protection by antibody transfer across the placenta. Notably, in high-income settings, many countries (starting in the 1990s) have switched to using the acellular pertussis vaccine, which is less reactogenic than (and therefore was thought to be preferable to) the older whole-cell pertussis vaccine that is still used in most low-income countries. It is now apparent that acellular pertussis vaccine induces a shorter duration of protection against clinical pertussis and may be less effective against bacterial transmission than is the whole-cell pertussis vaccine 47 . Many high-income countries have observed a rise in pertussis cases since the introduction of the acellular vaccine, a phenomenon that is not observed in low-income nations using the whole-cell vaccine 48 .

By contrast, lifelong protection seems to be the rule following a single dose with some of the live attenuated viral vaccines, such as yellow fever vaccine 49 (Fig.  4c ), although it is apparent that protection is incomplete with others. In the case of varicella zoster and measles–mumps vaccines, some breakthrough cases are described during disease outbreaks among those individuals who have previously been vaccinated, although it is unclear whether this represents a group in whom immunity has waned (and who therefore needed booster vaccination) or a group for whom the initial vaccine did not induce a successful immune response. Breakthrough cases are less likely in those individuals who have had two doses of measles–mumps–rubella vaccine 50 or varicella zoster vaccine 51 , and cases that do occur are usually mild, which indicates that there is some lasting immunity to the pathogen.

An illustration of the complexity of immune memory and the importance of understanding its underlying immunological mechanisms in order to improve vaccination strategies is provided by the concept of ‘original antigenic sin’. This phenomenon describes how the immune system fails to generate an immune response against a strain of a pathogen if the host was previously exposed to a closely related strain, and this has been demonstrated in several infections, including dengue 52 and influenza 53 . This might have important implications for vaccine development if only a single pathogen strain or pathogen antigen is included in a vaccine, as vaccine recipients might then have impaired immune responses if later exposed to different strains of the same pathogen, potentially putting them at increased risk of infection or more severe disease. Strategies to overcome this include the use of adjuvants that stimulate innate immune responses, which can induce sufficiently cross-reactive B cells and T cells that recognize different strains of the same pathogen, or the inclusion of as many strains in a vaccine as possible, the latter approach obviously being limited by the potential of new strains to emerge in the future 54 .

Herd immunity

Although direct protection of individuals through vaccination has been the focus of most vaccine development and is crucial to demonstrate for the licensure of new vaccines, it has become apparent that a key additional component of vaccine-induced protection is herd immunity, or more correctly ‘herd protection’ (Fig.  5 ). Vaccines cannot protect every individual in a population directly, as some individuals are not vaccinated for various reasons and others do not mount an immune response despite vaccination. Fortunately, however, if enough individuals in a population are vaccinated, and if vaccination prevents not only the development of disease but also infection itself (discussed in more detail below), transmission of the pathogen can be interrupted and the incidence of disease can fall further than would be expected, as a result of the indirect protection of individuals who would otherwise be susceptible.

The concept of herd immunity for a highly contagious disease such as measles. Susceptible individuals include those who have not yet been immunized (for example, being too young), those who cannot be immunized (for example, as a result of immunodeficiency), those for whom the vaccine did not induce immunity, those for whom initial vaccine-induced immunity has waned and those who refused immunization.

For highly transmissible pathogens, such as those causing measles or pertussis, around 95% of the population must be vaccinated to prevent disease outbreaks, but for less transmissible organisms a lower percentage of vaccine coverage may be sufficient to have a substantial impact on disease (for example, for polio, rubella, mumps or diphtheria, vaccine coverage can be ≤86%). For influenza, the threshold for herd immunity is highly variable from season to season and is also confounded by the variability in vaccine effectiveness each year 55 . Modest vaccine coverage, of 30–40%, is likely to have an impact on seasonal influenza epidemics, but ≥80% coverage is likely to be optimal 56 . Interestingly, there might be a downside to very high rates of vaccination, as the absence of pathogen transmission in that case will prevent natural boosting of vaccinated individuals and could lead to waning immunity if booster doses of vaccine are not used.

Apart from tetanus vaccine, all other vaccines in the routine immunization schedule induce some degree of herd immunity (Fig.  5 ), which substantially enhances population protection beyond that which could be achieved by vaccination of the individual only. Tetanus is a toxin-mediated disease acquired through infection of breaks in the skin contaminated with the toxin-producing bacteria Clostridium tetani from the environment — so, vaccination of the community with the tetanus toxoid will not prevent an unvaccinated individual acquiring the infection if they are exposed. As an example of the success of herd immunity, vaccination of children and young adults (up to 19 years of age) with capsular group C meningococcal vaccine in a mass campaign in 1999 resulted in almost complete elimination of disease from the UK in adults as well as children 57 . Currently, the strategy for control of capsular groups A, C, W and Y meningococci in the UK is vaccination of adolescents, as they are mainly responsible for transmission and vaccine-mediated protection of this age group leads to community protection through herd immunity 58 . The HPV vaccine was originally introduced to control HPV-induced cervical cancer, with vaccination programmes directed exclusively at girls, but it was subsequently found to also provide protection against HPV infection in heterosexual boys through herd immunity, which led to a marked reduction in the total HPV burden in the population 59 , 60 .

Prevention of infection versus disease

Whether vaccines prevent infection or, rather, the development of disease after infection with a pathogen is often difficult to establish, but improved understanding of this distinction could have important implications for vaccine design. BCG vaccination can be used as an example to illustrate this point, as there is some evidence for the prevention of both disease and infection. BCG vaccination prevents severe disease manifestations such as tuberculous meningitis and miliary TB in children 61 and animal studies have shown that BCG vaccination reduces the spread of M. tuberculosis bacteria in the blood, mediated by T cell immunity 62 , thereby clearly showing that vaccination has protective effects against the development of disease after infection. However, there is also good evidence that BCG vaccination reduces the risk of infection. In a TB outbreak at a school in the UK, 29% of previously BCG-vaccinated children had a memory T cell response to infection, as indicated by a positive interferon-γ release assay , as compared with 47% of the unvaccinated children 63 . A similar effect was seen when studying Indonesian household members of patients with TB, who had a 45% reduced chance of developing a positive interferon-γ release assay response to M. tuberculosis if they had previously been BCG vaccinated 64 . The lack of a T cell response in previously vaccinated individuals indicates that the BCG vaccine induces an innate immune response that results in ‘early clearance’ of the bacteria and prevents infection that induces an adaptive immune response. It will be hugely valuable for future vaccine development to better understand the induction of such protective innate immune responses so that they might be reproduced for other pathogens.

In the case of the current pandemic of the virus SARS-CoV-2, a vaccine that prevents severe disease and disease-driven hospitalization could have a substantial public health impact. However, a vaccine that could also block acquisition of the virus, and thus prevent both asymptomatic and mild infection, would have much larger impact by reducing transmission in the community and potentially establishing herd immunity.

Non-specific effects

Several lines of evidence indicate that immunization with some vaccines perturbs the immune system in such a way that there are general changes in immune responsiveness that can increase protection against unrelated pathogens 65 . This phenomenon has been best described in humans in relation to BCG and measles vaccines, with several studies showing marked reductions in all-cause mortality when these vaccines are administered to young children that are far beyond the expected impact from the reduction in deaths attributed to TB or measles, respectively 66 . These non-specific effects may be particularly important in high-mortality settings, but not all studies have identified the phenomenon. Although several immunological mechanisms have been proposed, the most plausible of which is that epigenetic changes can occur in innate immune cells as a result of vaccination, there are no definitive studies in humans that link immunological changes after immunization with important clinical end points, and it remains unclear how current immunization schedules might be adapted to improve population protection through non-specific effects. Of great interest in the debate, recent studies have indicated that measles disease casts a prolonged ‘shadow’ over the immune system, with depletion of existing immune memory, such that children who have had the disease have an increased risk of death from other causes over the next few years 67 , 68 . In this situation, measles vaccination reduces mortality from measles as well as the unconnected diseases that would have occurred during the ‘shadow’, resulting in a benefit that seems to be non-specific but actually relates directly to the prevention of measles disease and its consequences. This illustrates a limitation of vaccine study protocols: as these are usually designed to find pathogen-specific effects, the possibility of important non-specific effects cannot be assessed.

Factors affecting vaccine protection

The level of protection afforded by vaccination is affected by many genetic and environmental factors, including age, maternal antibody levels, prior antigen exposure, vaccine schedule and vaccine dose. Although most of these factors cannot be readily modified, age of vaccination and schedule of vaccination are important and key factors in planning immunization programmes. The vaccine dose is established during early clinical development, based on optimal safety and immunogenicity. However, for some populations, such as older adults, a higher dose might be beneficial, as has been shown for the influenza vaccine 69 , 70 . Moreover, intradermal vaccination has been shown to be immunogenic at much lower (fractional) doses than intramuscular vaccination for influenza, rabies and HBV vaccines 71 .

Age of vaccination

The highest burden of and mortality from infectious disease occur in the first 5 years of life, with the youngest infants being most affected. For this reason, immunization programmes have largely focused on this age group where there is the greatest benefit from vaccine-induced protection. Although this makes sense from an epidemiological perspective, it is somewhat inconvenient from an immunological perspective as the induction of strong immune responses in the first year of life is challenging. Indeed, vaccination of older children and adults would induce stronger immune responses, but would be of little value if those who would have benefited from vaccination have already succumbed to the disease.

It is not fully understood why immune responses to vaccines are not as robust in early infancy as they are in older children. One factor, which is increasingly well documented, is interference from maternal antibody 72 — acquired in utero through the placenta — which might reduce antigen availability, reduce viral replication (in the case of live viral vaccines such as measles 73 ) or perhaps regulate B cell responses. However, there is also evidence that there is a physiological age-dependent increase in antibody responses in infancy 72 . Furthermore, bone marrow niches to support B cells are limited in infancy, which might explain the very short-lived immune responses that are documented in the first year of life 74 . For example, after immunization with 2 doses of the capsular group C meningococcal vaccine in infancy, only 41% of infants still had protective levels of antibody by the time of the booster dose, administered 7 months later 75 .

In the case of T cell-independent antigens — in other words, plain polysaccharides from Hib, typhoid-causing bacteria, meningococci and pneumococci — animal data indicate that antibody responses depend on development of the marginal zone of the spleen, which is required for the maturation of marginal zone B cells, and this does not occur until around 18 months of age in human infants 76 . These plain polysaccharide vaccines do not induce memory B cells (Fig.  6 ) and, even in adults, provide protection for just 2–3 years, with protection resulting from antibody produced by plasma cells derived from marginal zone B cells 77 . However, converting plain polysaccharide vaccines into T cell-dependent protein–polysaccharide conjugate vaccines, which are immunogenic from 2 months of age and induce immune memory, has transformed prevention of disease caused by the encapsulated bacteria (pneumococci, Hib and meningococci) over the past three decades 78 . These are the most important invasive bacterial pathogens of childhood, causing most cases of childhood meningitis and bacterial pneumonia, and the development of the conjugate vaccine technology in the 1980s has transformed global child health 9 .

a | Polysaccharide vaccines induce antibody-producing plasma cells by cross-linking the B cell receptor (BCR). However, affinity maturation of the antibody response and the induction of memory B cells do not occur. b | Protein–polysaccharide conjugate vaccines can engage T cells that recognize the carrier protein, as well as B cells that recognize the polysaccharide. T cells provide help to B cells, leading to affinity maturation and the production of both plasma cells and memory B cells. TCR, T cell receptor. Adapted from ref. 35 , Springer Nature Limited.

Immune responses are also poor in the older population and most of the vaccines used in older adults offer limited protection or a limited duration of protection, particularly among those older than 75 years of age. The decline in immune function with age (known as immunosenescence) has been well documented 79 but, despite the burden of infection in this age group and the increasing size of the population, has not received sufficient attention so far amongst immunologists and vaccinologists. Interestingly, some have raised the hypothesis that chronic infection with cytomegalovirus (CMV) might have a role in immunosenescence through unfavourable effects on the immune system, including clonal expansion of CMV-specific T cell populations, known as ‘memory inflation’, and reduced diversity of naive T cells 80 , 81 .

In high-income countries, many older adults receive influenza, pneumococcal and varicella zoster vaccines, although data showing substantial benefits of these vaccines in past few decades in the oldest adults (more than 75 years of age) are lacking. However, emerging data following the recent development and deployment of new-generation, high-dose or adjuvanted influenza vaccines 82 and an adjuvanted glycoprotein varicella zoster vaccine 83 suggest that the provision of additional signals to the immune system by certain adjuvants (such as AS01 and MF59) can overcome immunosenescence. It is now necessary to understand how and why, and to use this knowledge to expand options for vaccine-induced protection at the extremes of life.

Schedule of vaccination

For most vaccines that are used in the first year of life, 3–4 doses are administered by 12 months of age. Conventionally, in human vaccinology, ‘priming’ doses are all those administered at less than 6 months of age and the ‘booster’ dose is given at 9–12 months of age. So, for example, the standard WHO schedule for diphtheria–tetanus–pertussis-containing vaccines (which was introduced in 1974 as part of the Expanded Programme on Immunization 84 ) consists of 3 priming doses at 6, 10 and 14 weeks of age with no booster. This schedule was selected to provide early protection before levels of maternal antibody had waned (maternal antibody has a half-life of around 30–40 days 85 , so very little protection is afforded to infants from the mother beyond 8–12 weeks of age) and because it was known that vaccine compliance is better when doses are given close together. However, infant immunization schedules around the world are highly variable — few high-income or middle-income countries use the Expanded Programme on Immunization schedule — and were largely introduced with little consideration of how best to optimize immune responses. Indeed, schedules that start later at 8–12 weeks of age (when there is less interference from maternal antibody) and have longer gaps between doses (8 weeks rather than 4 weeks) are more immunogenic. A large number of new vaccines have been introduced since 1974 as a result of remarkable developments in technology, but these have generally been fitted into existing schedules without taking into account the optimal scheduling for these new products. The main schedules used globally for diphtheria–tetanus–pertussis vaccine are presented in Supplementary Table 1 , and the changes to the UK immunization schedule since 1963 are presented in Supplementary Table 2 . It should also be noted that surveys show vaccines are rarely delivered on schedule in many countries and, thus, the published schedule may not be how vaccines are actually delivered on the ground. This is particularly the case in remote areas (for example, where health professionals only visit occasionally) and regions with limited or chaotic health systems, leaving children vulnerable to infection.

Safety and side effects of vaccines

Despite the public impression that vaccines are associated with specific safety concerns, the existing data indicate that vaccines are remarkably safe as interventions to defend human health. Common side effects, particularly those associated with the early innate immune response to vaccines, are carefully documented in clinical trials. Although rare side effects might not be identified in clinical trials, vaccine development is tightly controlled and robust post-marketing surveillance systems are in place in many countries, which aim to pick these up if they do occur. This can make the process of vaccine development rather laborious but is appropriate because, unlike most drugs, vaccines are used for prophylaxis in a healthy population and not to treat disease. Perhaps because vaccines work so well and the diseases that they prevent are no longer common, there have been several spurious associations made between vaccines and various unrelated health conditions that occur naturally in the population. Disentangling incorrect claims of vaccine harm from true vaccine-related adverse events requires very careful epidemiological studies.

Common side effects

Licensure of a new vaccine normally requires safety studies involving from 3,000 to tens of thousands of individuals. Thus, common side effects are very well known and are published by the regulator at the time of licensure. Common side effects of many vaccines include injection site pain, redness and swelling and some systemic symptoms such as fever, malaise and headache. All of these side effects, which occur in the first 1–2 days following vaccination, reflect the inflammatory and immune responses that lead to the successful development of vaccine-induced protection. About 6 days after measles–mumps–rubella vaccination, about 10% of 12-month-old infants develop a mild viraemia, which can result in fever and rash, and occasionally febrile convulsions (1 in 3,000) 86 . Although these side effects are self-limiting and relatively mild — and are trivial in comparison with the high morbidity and mortality of the diseases from which the vaccines protect — they can be very worrying for parents and their importance is often underestimated by clinicians who are counselling families about immunization.

Immunodeficiency and vaccination

Most vaccines in current use are inactivated, purified or killed organisms or protein and/or polysaccharide components of a pathogen; as they cannot replicate in the vaccine recipient, they are thus not capable of causing any significant side effects, resulting in very few contraindications for their use. Even in immunocompromised individuals, there is no risk from use of these vaccines, although the induction of immunity may not be possible, depending on the nature of the immune system defect. More caution is required for the use of live attenuated, replicating vaccines (such as yellow fever, varicella zoster, BCG and measles vaccines) in the context of individuals with T cell immunodeficiency as there is a theoretical risk of uncontrolled replication, and live vaccines are generally avoided in this situation 87 . A particular risk of note is from the yellow fever vaccine, which is contraindicated in individuals with T cell immunodeficiency and occasionally causes a severe viscerotropic or neurotropic disease in individuals with thymus disease or after thymectomy, in young infants and adults more than 60 years of age 88 . In individuals with antibody deficiency, there may be some merit in the use of routine live vaccines, as T cell memory may be induced that, although unlikely to prevent future infection, could improve control of the disease if infection occurs.

The myth of antigenic overload

An important parental concern is that vaccines might overwhelm their children’s immune systems. In a telephone survey in the USA, 23% of parents agreed with the statement ‘Children get more immunizations than are good for them’, and 25% indicated that they were concerned that their child’s immune system could be weakened by too many immunizations 89 . However, there is ample evidence to disprove these beliefs. Although the number of vaccines in immunization programmes has increased, the total number of antigens has actually decreased from more than 3,200 to approximately 320 as a result of discontinuing the smallpox vaccine and replacing the whole-cell pertussis vaccine with the acellular vaccine 90 , 91 . Vaccines comprise only a small fraction of the antigens that children are exposed to throughout normal life, with rapid bacterial colonization of the gastrointestinal tract after birth, multiple viral infections and environmental antigens. Moreover, multiple studies have shown that children who received vaccinations had a similar, or even reduced, risk of unconnected infections in the following period 92 , 93 , 94 , 95 . Looking at children who presented to the emergency department with infections not included in the vaccine programme, there was no difference in terms of their previous antigen exposure by vaccination 96 .

Significant rare side effects

Serious side effects from vaccines are very rare, with anaphylaxis being the most common of these rare side effects for parenteral vaccines , occurring after fewer than one in a million doses 97 . Individuals with known allergies (such as egg or latex) should avoid vaccines that may have traces of these products left over from the production process with the specific allergen, although most cases of anaphylaxis are not predictable in advance but are readily managed if vaccines are administered by trained health-care staff.

Very rare side effects of vaccines are not usually observed during clinical development, with very few documented, and they are only recognized through careful surveillance in vaccinated populations. For example, there is a very low risk of idiopathic thrombocytopenic purpura (1 in 24,000 vaccine recipients) after measles vaccination 86 . From 1 in 55,000 to 1 in 16,000 recipients of an AS03-adjuvanted 2009 pandemic H1N1 influenza vaccine 98 , 99 , who had a particular genetic susceptibility (HLA DQB1*0602) 100 , developed narcolepsy , although the debate continues about whether the trigger was the vaccine, the adjuvant or some combination, perhaps with the circulating virus also having a role.

Despite widespread misleading reporting about links between the measles–mumps–rubella vaccine and autism from the end of the 1990s, there is no evidence that any vaccines or their components cause autism 101 , 102 . Indeed, the evidence now overwhelmingly shows that there is no increased risk of autism in vaccinated populations. Thiomersal (also known as thimerosal) is an ethyl mercury-containing preservative that has been used widely in vaccines since the 1930s without any evidence of adverse events associated with it, and there is also no scientific evidence of any link between thiomersal and autism despite spurious claims about this 102 . Thiomersal has been voluntarily withdrawn from most vaccines by manufacturers as a precautionary measure rather than because of any scientific evidence of lack of safety and is currently used mainly in the production of whole-cell pertussis vaccines.

The risk of hospitalization, death or long-term morbidity from the diseases for which vaccines have been developed is so high that the risks of common local and systemic side effects (such as sore arm and fever) and the rare more serious side effects are far outweighed by the massive reductions in disease achieved through vaccination. Continuing assessment of vaccine safety post licensure is important for the detection of rare and longer-term side effects, and efficient reporting systems need to be in place to facilitate this 103 . This is particularly important in a pandemic situation, such as the COVID-19 pandemic, as rapid clinical development of several vaccines is likely to take place and large numbers of people are likely to be vaccinated within a short time.

Challenges to vaccination success

Vaccines only work if they are used. Perhaps the biggest challenge to immunization programmes is ensuring that the strong headwinds against deployment, ranging from poor infrastructure and lack of funding to vaccine hesitancy and commercial priorities, do not prevent successful protection of the most vulnerable in society. It is noteworthy that these are not classical scientific challenges, although limited knowledge about which antigens are protective, which immune responses are needed for protection and how to enhance the right immune responses, particularly in the older population, are also important considerations.

Access to vaccines

The greatest challenge for protection of the human population against serious infectious disease through vaccination remains access to vaccines and the huge associated inequity in access. Access to vaccines is currently limited, to varying degrees in different regions, by the absence of a health infrastructure to deliver vaccines, the lack of convenient vaccine provision for families, the lack of financial resources to purchase available vaccines (at a national, local or individual level) and the marginalization of communities in need. This is perhaps the most pressing issue for public health, with global vaccine coverage having stalled; for example, coverage for diphtheria–tetanus–pertussis-containing vaccines has only risen from 84% to 86% since 2010 (ref. 104 ). However, this figure hides huge regional variation, with near 100% coverage in some areas and almost no vaccinated children in others. For the poorest countries in the world, Gavi, the Vaccine Alliance provides funding to assist with new vaccine introductions and has greatly accelerated the broadening of access to new vaccines that were previously only accessible to high-income countries. However, this still leaves major financial challenges for countries that do not meet the criteria to be eligible for Gavi funding but still cannot afford new vaccines. Inequity remains, with approximately 14 million children not receiving any vaccinations and another 5.7 million children being only partially vaccinated in 2019 (ref. 105 ).

Other important issues can compromise vaccine availability and access. For example, most vaccines must be refrigerated at 2–8 °C, requiring the infrastructure and capacity for cold storage and a cold chain to the clinic where the vaccine is delivered, which is limited in many low-income countries. The route of administration can also limit access; oral vaccines (such as rotavirus, polio or cholera vaccines) and nasal vaccines (such as live attenuated influenza vaccine) can be delivered rapidly on a huge scale by less-skilled workers, whereas most vaccines are injected, which requires more training to administer and takes longer. Nevertheless, these hurdles can be overcome: in Sindh Province, Pakistan, 10 million doses of injected typhoid conjugate vaccine were administered to children to control an outbreak of extensively drug-resistant typhoid in just a few weeks at the end of 2019 (ref. 106 ).

The anti-vaccination movement

Despite access being the main issue affecting global vaccine coverage, a considerable focus is currently on the challenges posed by the anti-vaccination movement, largely as a result of worrying trends of decreasing vaccine coverage in high-income settings, leading to outbreaks of life-threatening infectious diseases, such as measles. In 2018, there were 140,000 deaths from measles worldwide, and the number of cases in 2019 was the highest in any year since 2006 (ref. 107 ). Much has been written about the dangerous role of social media and online search engines in the spread of misinformation about vaccines and the rise of the anti-vaccination movement, but scientists are also at fault for failing to effectively communicate the benefits of vaccination to a lay public. If this is to change, scientists do not need to counter or engage with the anti-vaccination movement but to use their expertise and understanding to ensure effective communication about the science that underpins our remarkable ability to harness the power of the immune system through vaccination to defend the health of our children.

Commercial viability

A third important issue is the lack of vaccines for some diseases for which there is no commercial incentive for development. Typically, these are diseases that have a restricted geographical spread (such as Rift Valley fever, Ebola, Marburg disease or plague) or occur in sporadic outbreaks and only affect poor or displaced communities (such as Ebola and cholera). Lists of outbreak pathogens have been published by various agencies including the WHO 108 , and recent funding initiatives, including those from US and European governments, have increased investment in the development of orphan vaccines . The Coalition for Epidemic Preparedness Innovations (CEPI) is set to have a major role in funding and driving the development of vaccines against these pathogens.

Immunological challenges

For other pathogens, there is likely to be a commercial market but there are immunological challenges for the development of new vaccines. For example, highly variable pathogens, including some with a large global distribution such as HIV and hepatitis C virus, pose a particular challenge. The genetic diversity of these pathogens, which occurs both between and within hosts, makes it difficult to identify an antigen that can be used to immunize against infection. In the case of HIV, antibodies can be generated that neutralize the virus, but the rapid mutation of the viral genome means that the virus can evade these responses within the same host. Some individuals do produce broadly neutralizing antibodies naturally, which target more conserved regions of the virus, leading to viral control, but it is not clear how to robustly induce these antibodies with a vaccine. Indeed, several HIV vaccines have been tested in clinical trials that were able to induce antibody responses (for example, RV144 vaccine showed 31% protection 109 ) and/or T cell responses, but these vaccines have not shown consistent evidence of protection in follow-up studies, and several studies found an increased risk of infection among vaccine recipients 110 .

For other pathogens, such as Neisseria gonorrhoeae (which causes gonorrhoea) and Treponema pallidum (which causes syphilis), antigenic targets for protective immune responses have not yet been determined, partly owing to limited investment and a poor understanding of the mechanisms of immunity at mucosal surfaces, or have thus far only resulted in limited protection. For example, the licensed malaria vaccine, RTSS, provides only 30–40% protection and further work is needed to develop suitable products 111 . New malaria vaccines in development target more conserved antigens on the parasite surface or target different stages of the parasite life cycle. Combinations of these approaches in a vaccine (perhaps targeting multiple stages of the life cycle), together with anti-vector strategies such as the use of genetically modified mosquitoes or Wolbachia bacteria to infect mosquitoes and reduce their ability to carry mosquito parasites 112 , as well as mosquito-bite avoidance, have the potential to markedly reduce malaria parasite transmission.

Seasonal influenza vaccines have, in recent decades, been used to protect vulnerable individuals in high-income countries, including older adults, children and individuals with co-morbidities that increase risk of severe influenza. These vaccines are made from virus that is grown in eggs; purified antigen, split virions or whole virions can be included in the final vaccine product. The vaccines take around 6 months to manufacture and have highly variable efficacy from one season to another, partly owing to the difficulty in predicting which virus strain will be circulating in the next influenza season, so that the vaccine strain may not match the strain causing disease 113 . Another issue that is increasingly recognized is egg adaptation, whereby the vaccine strain of virus becomes adapted to the egg used for production, leading to key mutations that mean it is not well matched to, and does not protect against, the circulating viral strain 114 . Vaccine-induced protection might be improved by the development of mammalian or insect cell-culture systems for growing influenza virus to avoid egg adaptation, and the use of MF59-adjuvanted vaccines and high-dose influenza vaccines to improve immune responses. Because of the cost of purchasing seasonal influenza vaccines annually, and the problem of antigenic variability, the search for a universal influenza vaccine receives considerable attention, with a particular focus on vaccines that induce T H cells or antibodies to conserved epitopes 115 , but there are currently no products in late-stage development.

Although BCG is the most widely used vaccine globally, with 89% of the world population receiving it in 2018 (ref. 105 ), there is still a huge global burden of TB and it is clear that more effective TB vaccines are needed. However, the optimal characteristics of a prophylactic TB vaccine, which antigens should be included and the nature of protective immunity remain unknown, despite more than 100 years of TB vaccine research. A viral vector expressing a TB protein, 85A, has been tested in a large TB-prevention trial in South Africa but this vaccine did not show protection, which was attributed by the authors to poor immunogenicity in the vaccinated children 116 . However, the publication of a study in 2019 showing that a novel TB vaccine, M72/AS01E (an AS01-adjuvanted vaccine containing the M. tuberculosis antigens MTB32A and MTB39A), could limit progression to active TB disease in latently infected individuals with efficacy of 50% over 3 years gives a glimmer of hope that TB control may be realized in the future by novel vaccine approaches 117 . Questions remain about the duration of the effect, but the demonstrated efficacy can now be interrogated thoroughly to determine the nature of protective immunity against TB.

Future vaccine development

There are several important diseases for which new vaccines are needed to reduce morbidity and mortality globally, which are likely to have a market in both high-income and low-income countries, including vaccines for group B Streptococcus (a major cause of neonatal meningitis), RSV and CMV. Group B Streptococcus vaccines are currently in trials of maternal vaccination, with the aim of inducing maternal antibodies that cross the placenta and protect the newborn passively 118 . RSV causes a lower respiratory tract infection, bronchiolitis, in infancy and is the commonest cause of infant hospitalization in developed countries and globally one of the leading causes of death in those less than 12 months of age. As many as 60 new RSV vaccine candidates are in development as either maternal vaccines or infant vaccines, or involving immunization with RSV-specific monoclonal antibodies that have an extended half-life. A licensed RSV vaccine would have a huge impact on infant health and paediatric hospital admissions. CMV is a ubiquitous herpesvirus that is responsible for a significant burden of disease in infants; 15–20% of congenitally infected children develop long-term sequelae, most importantly sensorineural hearing loss, and CMV thus causes more congenital disease than any other single infectious agent. A vaccine that effectively prevents congenital infection would provide significant individual and public health benefits. A lack of understanding of the nature of protective immunity against CMV has hampered vaccine development in the past, but the pipeline is now more promising 119 , 120 .

Another major line of development of new vaccines is to combat hospital-acquired infections, particularly with antibiotic-resistant Gram-positive bacteria (such as Staphylococcus aureus ) that are associated with wound infections and intravenous catheters and various Gram-negative organisms (such as Klebsiella spp. and Pseudomonas aeruginosa ). Progress has been slow in this field and an important consideration will be targeting products to the at-risk patient groups before hospital admission or surgery.

Perhaps the largest area of growth for vaccine development is for older adults, with few products aimed specifically at this population currently. With the population of older adults set to increase substantially (the proportion of the population who are more than 60 years of age is expected to increase from 12% to 22% by 2050 (ref. 121 )), prevention of infection in this population should be a public health priority. Efforts to better understand immunosenescence and how to improve vaccine responses in the oldest adults are a major challenge for immunologists today.

Novel technologies

Important challenges to overcome in the following years are genetic diversity (for example, of viruses such as HIV, hepatitis C virus and influenza), the requirement for a broader immune response including T cells for protection against diseases such as TB and malaria, and the need to swiftly respond to emerging pathogens and outbreak situations. Traditionally, vaccine development takes more than 10 years 122 , but the COVID-19 pandemic has demonstrated the urgency for vaccine technologies that are flexible and facilitate rapid development, production and upscaling 123 .

Novel technologies to combat these hurdles will include platforms that allow for improved antigen delivery and ease and speed of production, application of structural biology and immunological knowledge to aid enhanced antigen design and discovery of better adjuvants to improve immunogenicity. Fortunately, recent advances in immunology, systems biology, genomics and bio-informatics offer great opportunities to improve our understanding of the induction of immune responses by vaccines and to transform vaccine development through increasingly rational design 124 .

New platforms include viral vectored vaccines and nucleic acid-based vaccines. Antigen-presenting cells such as dendritic cells, T cell-based vaccines and bacterial vectors are being explored as well, but are still at early stages of development for use against infectious pathogens. Whereas classic whole-organism vaccine platforms require the cultivation of the pathogen, next-generation viral vectored or nucleic acid-based vaccines can be constructed using the pathogen genetic sequence only, thereby significantly increasing the speed of development and manufacturing processes 125 .

Viral vectored vaccines are based on a recombinant virus (either replicating or not), in which the genome is altered to express the target pathogen antigen. The presentation of pathogen antigens in combination with stimuli from the viral vector that mimic natural infection leads to the induction of strong humoral and cellular immune responses without the need for an adjuvant. A potential disadvantage of viral vectored vaccines is the presence of pre-existing immunity when a vector such as human adenovirus is used that commonly causes infection in humans. This can be overcome by using vectors such as a simian adenovirus, against which almost no pre-existing immunity exists in humans 126 . Whether immune responses against the vector will limit its use for repeated vaccinations with different antigens will need to be investigated.

Nucleic acid-based vaccines consist of either DNA or RNA encoding the target antigen, which potentially allows for the induction of both humoral and cellular immune responses once the encoded antigens are expressed by the vaccine recipient after uptake of the nucleic acid by their cells. A huge advantage of these vaccines is that they are highly versatile and quick and easy to adapt and produce in the case of an emerging pathogen. Indeed, the SARS-CoV-2 mRNA-based vaccine mRNA-1273 entered clinical testing just 2 months after the genetic sequence of SARS-CoV-2 was identified 127 and the BNT162b2 lipid nanoparticle-formulated, nucleoside-modified RNA vaccine was the first SARS-CoV-2 vaccine to be licensed 128 . One of the disadvantages of these vaccines is that they need to be delivered directly into cells, which requires specific injection devices, electroporation or a carrier molecule and brings with it a risk of low transfection rate and limited immunogenicity 129 . Furthermore, the application of RNA vaccines has been limited by their lack of stability and requirement for a cold chain, but constant efforts to improve formulations hold promise to overcome these limitations 130 , 131 .

A beautiful example of how immunological insight can revolutionize vaccine development is the novel RSV vaccine DS-Cav1. The RSV surface fusion (F) protein can exist in either a pre-fusion (pre-F) conformation, which facilitates viral entry, or a post-fusion (post-F) form. Whereas previous vaccines mainly contained the post-F form, insight into the atomic-level structure of the protein has allowed for stable expression of the pre-F protein, leading to strongly enhanced immune responses and providing a proof of concept for structure-based vaccine design 132 , 133 .

In addition to the novel vaccine platforms mentioned above, there are ongoing efforts to develop improved methods of antigen delivery, such as liposomes (spherical lipid bilayers), polymeric particles, inorganic particles, outer membrane vesicles and immunostimulating complexes. These, and other methods such as self-assembling protein nanoparticles, have the potential to optimally enhance and skew the immune response to pathogens against which traditional vaccine approaches have proven to be unsuccessful 129 , 134 . Furthermore, innovative delivery methods, such as microneedle patches, are being developed, with the potential advantages of improved thermostability, ease of delivery with minimal pain and safer administration and disposal 135 . An inactivated influenza vaccine delivered by microneedle patch was shown to be well tolerated and immunogenic in a phase I trial 136 . This might allow for self-administration, although it would be important for professional medical care to be available if there is a risk of severe side effects such as anaphylaxis.

Conclusions and future directions

Immunization protects populations from diseases that previously claimed the lives of millions of individuals each year, mostly children. Under the United Nations Convention on the Rights of the Child, every child has the right to the best possible health, and by extrapolation a right to be vaccinated.

Despite the outstanding success of vaccination in protecting the health of our children, there are important knowledge gaps and challenges to be addressed. An incomplete understanding of immune mechanisms of protection and the lack of solutions to overcome antigenic variability have hampered the design of effective vaccines against major diseases such as HIV/AIDS and TB. Huge efforts have resulted in the licensure of a partially effective vaccine against malaria, but more effective vaccines will be needed to defeat this disease. Moreover, it is becoming clear that variation in host response is an important factor to take into account. New technologies and analytical methods will aid the delineation of the complex immune mechanisms involved, and this knowledge will be important to design effective vaccines for the future.

Apart from the scientific challenges, sociopolitical barriers stand in the way of safe and effective vaccination for all. Access to vaccines is one of the greatest obstacles, and improving infrastructure, continuing education and enhancing community engagement will be essential to improve this, and novel delivery platforms that eliminate the need for a cold chain could have great implications. There is a growing subset of the population who are sceptical about vaccination and this requires a response from the scientific community to provide transparency about the existing knowledge gaps and strategies to overcome these. Constructive collaboration between scientists and between scientific institutions, governments and industry will be imperative to move forwards. The COVID-19 pandemic has indeed shown that, in the case of an emergency, many parties with different incentives can come together to ensure that vaccines are being developed at unprecedented speed but has also highlighted some of the challenges of national and commercial interests. As immunologists, we have a responsibility to create an environment where immunization is normal, the science is accessible and robust, and access to vaccination is a right and expectation.

Change history

05 january 2021.

A Correction to this paper has been published: https://doi.org/10.1038/s41577-020-00497-5.

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Acknowledgements

The authors thank all those whose work in the development, policy and delivery of vaccines underpins immunization programmes to defend our health and the health of our children.

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A.J.P. is Chair of the UK Department of Health and Social Care’s (DHSC) Joint Committee on Vaccination and Immunisation (JCVI), a member of the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE) and a National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article do not necessarily represent the views of the DHSC, JCVI, NIHR or WHO. E.M.B. declares no competing interests. Oxford University has entered into a partnership with AstraZeneca for the development of a viral vectored coronavirus vaccine.

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Supplementary information

Supplementary information.

Parts of the pathogen (such as proteins or polysaccharides) that are recognized by the immune system and can be used to induce an immune response by vaccination.

The state in which an individual does not develop disease after being exposed to a pathogen.

A reduction in the virulence of a pathogen (through either deliberate or natural changes in virulence genes).

Particles constructed of viral proteins that structurally mimic the native virus but lack the viral genome.

An agent used in a vaccine to enhance the immune response against the antigen.

Molecules that stimulate a more robust immune response together with an antigen. Endogenous mediators that are released in response to infection or injury and that interact with pattern recognition receptors such as Toll-like receptors to activate innate immune cells such as dendritic cells.

The evolutionarily primitive part of the immune system that detects foreign antigens in a non-specific manner.

A liposome-based adjuvant containing 3- O -desacyl-4′-monophosphoryl lipid A and the saponin QS-21. AS01 triggers the innate immune system immediately after vaccination, resulting in an enhanced adaptive immune response.

An adjuvant consisting of aluminium salt and the Toll-like receptor agonist monophosphoryl lipid A.

A network of proteins that form an important part of the immune response by enhancing the opsonization of pathogens, cell lysis and inflammation.

A state of a pathogen in which antibodies or complement factors are bound to its surface.

Antibodies that bind to a pathogen, which subsequently can be eliminated by phagocytosis.

Antigens against which B cells can mount an antibody response without T cell help.

An antigen for which T cell help is required in order for B cells to mount an antibody response.

Studies in which volunteers are deliberately infected with a pathogen, in a carefully conducted study, to evaluate the biology of infection and the efficacy of drugs and vaccines.

The capacity of the immune system to respond quicker and more effectively when a pathogen is encountered again after an initial exposure that induced antigen-specific B cells and T cells.

The period from acquisition of a pathogen to the development of symptomatic disease.

Repeat administration of a vaccine after an initial priming dose, given in order to enhance the immune response.

An assay in which blood is stimulated with Mycobacterium tuberculosis antigens, after which levels of interferon-γ (produced by specific memory T cells if these are present) are measured.

Changes in the expression of genes that do not result from changes in DNA sequence.

A severe and potentially life-threatening reaction to an allergen.

Vaccines that are administered by means avoiding the gastrointestinal tract (for example, by intramuscular, subcutaneous or intradermal routes).

An acquired autoimmune condition characterized by low levels of platelets in the blood caused by antibodies to platelet antigens.

A rare chronic sleep disorder characterized by extreme sleepiness during the day and sudden sleep attacks.

Vaccines that are intended for a limited scope or targeting infections that are rare, as a result of which development costs exceed their market potential.

Blebs made from the outer membrane of Gram-negative bacteria, containing the surface proteins and lipids of the organism in the membrane.

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Pollard, A.J., Bijker, E.M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol 21 , 83–100 (2021). https://doi.org/10.1038/s41577-020-00479-7

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29 July 2024

Issued: London, UK and Cambridge MA

For media and investors only

GSK and Flagship Pioneering partner to discover novel medicines and vaccines

• Collaboration brings together GSK disease area expertise and development capability with Flagship portfolio of 40+ bioplatform companies
• Initial phase to identify and accelerate promising scientific concepts for further research starting in respiratory and immunology
• GSK and Flagship to jointly fund up to $150 million upfront

GSK plc (LSE/NYSE: GSK) and Flagship Pioneering (Flagship), the bioplatform innovation company, today announced they have entered a collaboration with the goal of discovering and developing a portfolio of future transformational medicines and vaccines, starting in respiratory and immunology.

This alliance brings together GSK’s disease area expertise and development capability with Flagship’s ecosystem of bioplatform companies, inclusive of its novel modalities and technologies, to make major advances in healthcare.

GSK and Flagship will initially fund up to $150 million upfront to support an exploration phase to identify the most promising concepts for further research and development with Flagship’s bioplatform companies. From these explorations, the collaboration aims to identify a portfolio of up to 10 novel medicines and vaccines which will each be subject to an exclusive option by GSK for further clinical development. Under the terms of the agreement, Flagship and its bioplatform companies will be eligible to receive up to $720 million in upfront, development and commercial milestones from GSK, as well as preclinical funding and tiered royalties, for each acquired programme.

Tony Wood, Chief Scientific Officer, GSK, said: “Together with Flagship, we will use science and technology to deliver best-in-class innovation at pace. We look forward to partnering with the talented team at Flagship, and their ecosystem of bioplatform companies, to further accelerate our pipeline and discover practice-changing medicines and vaccines for patients.”

Paul Biondi, General Partner, Flagship Pioneering and President, Pioneering Medicines, said:  “Flagship and GSK have a shared focus on delivering breakthrough medicines for patients. This collaboration is the latest example of Flagship’s Innovation Supply Chain Partnership model, which is designed to generate transformational medicines together with our pharma partners by leveraging our ecosystem of first-in-category bioplatforms to create a sustainable source of treatments for patients with the greatest unmet needs.”

About Flagship Pioneering

Flagship Pioneering invents and builds bioplatform companies, each with the potential for multiple products that transform human health or sustainability. Since its launch in 2000, Flagship has originated and fostered more than 100 scientific ventures, resulting in more than $75 billion in aggregate value. To date, Flagship has deployed over $3.8 billion in capital toward the founding and growth of its pioneering companies alongside more than $27 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 40 companies, including  Foghorn Therapeutics  (NASDAQ: FHTX),  Moderna  (NASDAQ: MRNA), Omega Therapeutics  (NASDAQ: OMGA),  Sana Biotechnology  (NASDAQ: SANA),  Generate Biomedicines ,  Inari ,  Indigo Agriculture ,  and  Tessera Therapeutics .

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D “Risk factors” in GSK’s Annual Report on Form 20-F for 2023, and GSK’s Q1 Results for 2024.

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We are a global biopharma company with a purpose to unite science, technology and talent to get ahead of disease together

CSL Seqirus Proud to Attend and Present at 2023 Canadian Immunization Conference

Csl seqirus, a global leader in influenza prevention, announced the presentation of data from two canadian studies at the 2023 canadian immunization conference in ottawa, ontario..

Experts and public health leaders gather at annual conference in Ottawa to discuss the importance and future of immunization in Canada

MONTREAL, April 25, 2023 /CNW/ - CSL Seqirus , a global leader in influenza prevention, announced today the presentation of data from two Canadian studies at the 2023 Canadian Immunization Conference (CIC) in Ottawa, Ontario:

• A literature review of vaccine effectiveness of enhanced seasonal influenza vaccines in older adults; and
• A survey investigating pediatric influenza vaccination perceptions and uptake motivations and barriers.

Held from April 25-27, 2023, CIC brings together experts and thought-provoking speakers for a scientific program that engages and inspires future research, policies and practices.

“Every year, CIC is a key opportunity for leading experts to gather and discuss advancements in immunization,” said Bertrand Roy, Country Head Medical Affairs, CSL Seqirus. “This is especially important this year, as we debrief on key learnings from a very challenging flu season and align on ways to help prevent similar seasons moving forward.”

A systematic literature review and meta-analysis comparing relative vaccine effectiveness of enhanced trivalent seasonal influenza vaccines in older adults Brenda Coleman, Ian McGovern, Mendel Haag (Poster Exhibition: April 25, 2023 at 1:50-2:50 p.m. EST and April 26, 2023 at 1:50-2:50 p.m. EST)

Dr. Brenda Coleman, PhD, Infectious Disease Epidemiology Research Unit, Mount Sinai Hospital, will present the results of a literature review conducted over 4 seasons that reports on relative vaccine effectiveness (rVE) of adjuvanted vaccines (aTIV) in comparison to high-dose vaccines (HD-TIV) for older adults (≥ 65 years of age).

The literature review and meta-analysis suggest that aTIV and HD-TIV have comparable vaccine performance for prevention of influenza-related outpatient and hospital and emergency department visits.

“Access to the appropriate type of vaccines for older adults is critical to help prevent severe illness and other complications caused by influenza,” says Dr. Coleman. “Older adults are at a greater risk due to the age-associated decline of their immune system. Therefore, it is important that they receive an enhanced (either an aTIV or HD-TIV) vaccine since they offer better protection against the flu compared to standard influenza vaccines.”

Parental attitudes and perceptions regarding pediatric influenza vaccination in Canada and the role of health care providers Wendy Boivin, Rupesh Chawla, Ajit Johal and Bertrand Roy (Poster Exhibition: April 25, 2023 at 1:50-2:50 p.m. EST and April 26, 2023 at 1:50-2:50 p.m. EST)

Dr. Wendy Boivin, PhD, Senior Medical Science Liaison, CSL Seqirus, will present the results of a national online survey conducted in 2022 to evaluate parental perceptions and behaviors towards pediatric influenza vaccination.

Including responses from 1,500 parents of children aged 6 months to 17 years, the results suggest that low pediatric vaccination was heavily influenced by the parents’ own vaccination status:

• Among parents who get vaccinated every year, 70% report they also vaccinate their children annually. In comparison, among parents who get vaccinated less frequently, only 17% said they vaccinate their children every year.
• 51% of parents who plan on occasionally getting their child vaccinated against the flu say they are interested in learning about effectiveness, side-effects and potential interactions with COVID-19 vaccines.

Further, while less than half of respondents (44%) recalled discussing influenza vaccination for their children with a healthcare provider, respondents who did speak to a healthcare provider reported they were more likely to have their child vaccinated. This suggests that healthcare providers who proactively recommend influenza vaccination to parents have a direct impact on vaccination rates.

Influenza is a common, contagious seasonal respiratory disease and can cause mild to severe illness, which can result in hospitalization or death. 1 Adults may spread influenza to others from 1 day before symptoms begin to approximately 5 days after symptoms start. 1 Children and people with weakened immune systems may be infectious longer.

Influenza is related to an average of 12,200 hospitalizations and approximately 3,500 deaths each year in Canada. 1 Canada’s National Advisory Committee on Immunization (NACI) recommends annual influenza vaccination for all individuals six months of age and older. 1 Further, NACI recommends including all children between 6 and 59 months of age among the particularly recommended recipients of the influenza vaccine. 1

NACI recommends that healthcare providers in Canada offer the seasonal influenza vaccine as soon as feasible after it becomes available in the fall, since seasonal influenza activity may start as early as October in the Northern Hemisphere. 1

CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL .

For more information about CSL, visit www.CSL.com .

This press release is issued from CSL Seqirus in Montreal, Quebec, Canada and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved CSL Seqirus products may vary from country to country. Please consult your local regulatory authority on the approval status of CSL Seqirus products.

This press release may contain forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements.

For further information, please contact:

Tiffany Cody +1 (908) 370-1863 [email protected]

Anna Tejada +1 (437) 855-5947 [email protected]

SOURCE CSL Seqirus

Company Codes: Australia:CSL, OTC-PINK:CSLLY, OTC-BB:CSLLY

News 07.29.2024

GSK and Flagship Pioneering partner to discover novel medicines and vaccines

• Share on LinkedIn
• Share on Twitter

Collaboration brings together GSK disease area expertise and development capability with Flagship portfolio of 40+ bioplatform companies

Initial phase to identify and accelerate promising scientific concepts for further research starting in respiratory and immunology

GSK and Flagship to jointly fund up to $150 million upfront

LONDON and CAMBRIDGE, Mass., July 29, 2024 – GSK plc (LSE/NYSE: GSK) and Flagship Pioneering (Flagship), the bioplatform innovation company, today announced they have entered a collaboration with the goal of discovering and developing a portfolio of future transformational medicines and vaccines, starting in respiratory and immunology.

This alliance brings together GSK’s disease area expertise and development capability with Flagship’s ecosystem of bioplatform companies, inclusive of its novel modalities and technologies, to make major advances in healthcare.

GSK and Flagship will initially fund up to $150 million upfront to support an exploration phase to identify the most promising concepts for further research and development with Flagship’s bioplatform companies. From these explorations, the collaboration aims to identify a portfolio of up to 10 novel medicines and vaccines which will each be subject to an exclusive option by GSK for further clinical development. Under the terms of the agreement, Flagship and its bioplatform companies will be eligible to receive up to $720 million in upfront, development and commercial milestones from GSK, as well as preclinical funding and tiered royalties, for each acquired programme.

Tony Wood, Chief Scientific Officer, GSK, said: “Together with Flagship, we will use science and technology to deliver best-in-class innovation at pace. We look forward to partnering with the talented team at Flagship, and their ecosystem of bioplatform companies, to further accelerate our pipeline and discover practice-changing medicines and vaccines for patients.”

Paul Biondi , General Partner, Flagship Pioneering and President, Pioneering Medicines, said: “Flagship and GSK have a shared focus on delivering breakthrough medicines for patients. This collaboration is the latest example of Flagship’s Innovation Supply Chain Partnership model, which is designed to generate transformational medicines together with our pharma partners by leveraging our ecosystem of first-in-category bioplatforms to create a sustainable source of treatments for patients with the greatest unmet needs.”

About Flagship Pioneering

Flagship Pioneering invents and builds bioplatform companies, each with the potential for multiple products that transform human health or sustainability. Since its launch in 2000, Flagship has originated and fostered more than 100 scientific ventures, resulting in more than $75 billion in aggregate value. To date, Flagship has deployed over $3.8 billion in capital toward the founding and growth of its pioneering companies alongside more than $27 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 40 companies, including  Foghorn Therapeutics  (NASDAQ: FHTX), Moderna  (NASDAQ: MRNA), Omega Therapeutics (NASDAQ: OMGA),  Sana Biotechnology  (NASDAQ: SANA),  Generate Biomedicines ,  Inari ,  Indigo Agriculture ,  and  Tessera Therapeutics .

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

Flagship enquiries [email protected] GSK enquiries Media: Tim Foley, +44 (0) 20 8047 5502 (London) Sarah Clements, +44 (0) 20 8047 5502 (London) Kathleen Quinn, +1 202 603 5003 (Washington DC) Sydney Dodson-Nease, +1 215 370 4680 (Philadelphia)

Investor Relations: Nick Stone, +44 (0) 7717 618834 (London) James Dodwell, +44 (0) 20 8047 2406 (London) Mick Readey, +44 (0) 7990 339653 (London) Josh Williams, +44 (0) 7385 415719 (London) Camilla Campbell, +44 (0) 7803 050238 (London) Steph Mountifield, +44 (0) 7796 707505 (London) Jeff McLaughlin, +1 215 751 7002 (Philadelphia) Frannie DeFranco, +1 215 751 4855 (Philadelphia)

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ACIP Presentation Slides: September 22, 2023 Meeting

Note: These files are not yet 508

Slides will be added as they become available.

September 22, 2023

Welcome & introductions.

• Introduction Dr. G Lee Dr. M Wharton

RSV Vaccines

• Introduction [14 pages] Dr. S Long
• RSVpreF Vaccine Safety Surveillance in Pregnancy from The Vaccine Safety Datalink [19 pages] Dr. M DeSilva
• Maternal RSV vaccine safety monitoring in the VAERS and V-safe [10 pages] Dr. P Moro
• Economic analysis of RSVpreF maternal vaccination [87 pages] Dr. D Hutton
• Economics of Preventing RSV Disease among US Infants by Maternal Vaccination Prior to Birth [25 pages] Dr. I Ortega-Sanchez
• EtR Framework Updates: Pfizer Maternal RSVpreF Vaccine [139 pages] Dr. K Fleming-Dutra
• Updated clinical considerations for use of both nirsevimab and Pfizer RSVpreF vaccine [19 pages] Dr. J Jones
• Implementation considerations for maternal RSV vaccine [17 pages] Dr. G Peacock
• Adult and Pediatric Immunization Schedule Addendum [32 pages] Dr. S Schillie