Vaccination and, in particular, multiple vaccinations

1. Introduction

    Vaccines defend against infections by priming the natural defense mechanisms of the body. Vaccination has enabled us to reduce most vaccine-preventable diseases to very low levels in many countries and even, in the case of smallpox, to completely eradicate it. However, some of them are still quite prevalent — even epidemic — in some parts of the world. Travellers can unknowingly bring these diseases into any country, and if the community were not protected by vaccinations, these diseases could quickly spread throughout the population, causing epidemics there.

    Vaccination is one of the most cost-effective health interventions available, saving millions of people from illness, disability and death each year. Effective and safe vaccines, which protect against a number of serious diseases, are available and many promising new vaccines are being developed2. Like the case of a driver having to respect all traffic regulations in order to ensure not only his own safety, but everyone else’s, a successful vaccination program, like a successful society, depends on the cooperation of every individual for the good of all. The higher the vaccination coverage, the more the circulation of the bacterium or virus concerned is reduced and the number of cases in vaccinated and unvaccinated patients is reduced in the general population. But there is a minimum threshold of immunization coverage for this group immunity to work. This threshold depends on the contagiousness of the disease.

    In France, with a vaccination coverage of nearly 97% for diphtheria, the threshold for group immunity is exceeded and the entire community is protected. Nevertheless, driven largely by concerns about potential side effects, there has been a shift in some parents’ attitudes toward the child immunization schedule. Vaccine hesitancy is indeed becoming a global threat to immunization programmes. Confidence in vaccine safety is less positive, particularly in the European region, which, compared to a global average of 12%, has seven of the ten least confident countries, with only 41% of respondents in France and 36% of respondents in Bosnia & Herzegovina reporting that they disagree that vaccines are safe, followed by Russia (28%) and Mongolia (27%), with Greece, Japan and Ukraine not far behind (25%).

    A number of concerned parents say the schedule is too “crowded” and have requested flexibility, such as delaying one or more immunizations or having fewer shots per visit. Some parents have rejected the vaccines outright, arguing that the potential harm of their child suffering a side effect from the vaccine outweighs the well-documented benefits of immunizations preventing serious disease.

    Other parents delay or decline immunizations due to worries that family history, the child’s premature birth, or an underlying medical condition may make them more vulnerable to complications. Some just distrust the federal government’s decisions about the safety and benefits of childhood immunizations.


    2. What is a vaccine?

      There are several different types of vaccines. Each type is designed to teach our immune system how to fight off certain kinds of germs — and the serious diseases they cause.

      Vaccines contain weakened, killed, or parts of the germs that cause a disease. These elements of vaccines, and other molecules and micro-organisms that stimulate the immune system, are called “antigens.”

      Babies are exposed to thousands of germs and other antigens in the environment from the time they are born. When a baby is born, his or her immune system is ready to respond to the many antigens that are present in their environment, and the selected antigens in vaccines.

      After receiving the vaccine, if the virus or bacteria that cause the real disease enters the body in the future, the immune system is prepared and responds quickly and forcefully to attack the disease-causing agent to prevent the person from getting sick. A certain type of white blood cells (called B-lymphocytes) create many copies of a protein called an “antibody” that is precisely designed to react with and inhibit that antigen. If a true infection with the same germ occurs later on, still more antibodies are created, and as they attach to their targets they may block the activity of the virus or bacterial strain directly, thus combating infection.

      3. Are there different types of vaccines?

        There are 4 main types of vaccines:

        1. Live-attenuated vaccines: Because these vaccines, used a.o. to protect against measles, mumps, rubella (MMR combined vaccine), rotavirus or yellow fever, are so similar to the natural infection that they help prevent, they create a strong and long-lasting immune response. Just 1 or 2 doses of most live vaccines can give you a lifetime protection against a germ and the disease it causes.
        2. Inactivated vaccines, which usually are used to protect against hepatitis A, influenza, rabies or poliomyelitis don’t provide immunity (protection) as strong as live vaccines. Therefore, several doses may be needed over time (booster shots) in order to get ongoing immunity against diseases.
        3. Vaccines using specific pieces of the germ — like its protein, sugar, or capsid (a casing around the germ) are called subunit, recombinant, polysaccharide, and conjugate vaccines. They give a very strong immune response that’s targeted to key parts of the germ and are used to protect against e.g. Haemophilus influenza type b, hepatitis B, Human papilloma virus, pneumocccal an meningoccocal diseases. They can be used on almost everyone who needs them, including people with weakened immune systems and long-term health problems. One limitation of these vaccines is that booster shots may be needed to get ongoing protection against diseases.
        4. Toxoid vaccines, which use a harmful product (called toxin) that is made by the germ that causes a disease. They protect against diphteria an tetanos by creating immunity to the specific parts of the germ that cause a disease, instead of the germ.

        Vaccines are frequently given by injection (a shot), but some are given by mouth or, rarely, can be sprayed into the nose.

        4. Why should children in particular be vaccinated?

          As explained by the US Center for Disease control (CDC), children are given shots (vaccines) at a young age because this is when they are at highest risk of getting sick or dying if they get these diseases. From the time they are born, babies in particular, are exposed on a daily basis to thousands of germs and other antigens in the environment.

          Eating food, for example, introduces new bacteria into the body; numerous bacteria live in the mouth and nose, and an infant places his or her hands or other objects in his or her mouth hundreds of times every hour, exposing the immune system to still more germs. When a child has a cold, he or she is exposed to up to 10 antigens and exposure to “strep throat” is about 25 to 50 antigens.

          When a baby is born, his or her immune system is ready to respond to the many antigens in the environment and the selected antigens present in vaccines. They are protected (immune) to some diseases because they have antibodies they got from their mothers, usually before they are born. However, this immunity lasts only a few months, and most babies do not get protective antibodies against diphtheria, whooping cough, polio, tetanus, hepatitis B, or Haemophilus influenza type B (Hib) from their mothers. This is why it is important to vaccinate a child before she or he is exposed to a disease.

          In the USA, the CDC recommends vaccinations before the age of two years to protect children against 14 infectious diseases3 : measles, mumps, rubella (German measles), varicella (chickenpox), hepatitis A, hepatitis B, diphtheria, tetanus, pertussis (whooping cough), Haemophilus influenza type B (Hib), poliomyelitis, influenza (flu), rotavirus, and pneumococcal disease. It is important to notice that vaccines are given to healthy children also to protect others in addition to themselves, and so to avoid epidemics. Parents generally worry about children’s health and well-being, and their concerns about immunization safety can be viewed in that context. However, delaying or declining vaccination has led to outbreaks of vaccine-preventable diseases such as measles and whooping cough that may jeopardize public health, particularly for people who are under-immunized or who were never immunized.


          5. What is the degree of efficacy of vaccines?

            The Institut National de la Santé et de la Recherche Médicale (INSERM) recently published data on the efficacy of the 11 vaccines that will be mandatory in France for children. According to INSERM, they protect against disease 90% or more:

            • Poliomyelitis: vaccine already compulsory, more than 90% of effectiveness;
            • Tetanus: vaccine already compulsory, protection up to 100%;
            • Diphtheria: vaccine already mandatory, 96 to 98% effectiveness in infants - whooping cough: efficacy between 85 and 90%;
            • Measles: vaccine effective at nearly 100% after 2 doses of vaccine ;
            • Mumps: effectiveness of vaccination greater than 90%;
            • Rubella: protection close to 100%;
            • Hepatitis B: concentrations Antibody Protectors in more than 95% of Infants;
            • Haemophilus Meningitis influenzae b: close to 100% protection;
            • Pneumonia, meningitis and sepsis Pneumococcus (13-valent conjugate vaccine): infant protection greater than 90%;
            • Meningitis and meningococcal sepsis C: efficacy greater than 90%.

            6. Why is the vaccination of young girls against the human papillomavirus (HPV) particularly promoted?

              The human papillomavirus (HPV) vaccine is a key strategy for comprehensive cervical cancer control and prevention. By the end of 2015, more than 65 countries introduced HPV vaccine into their national immunization programmes.

              HPV vaccine is targeting girls before they become sexually active in order to prevent acquisition of a sexually transmitted infection (STI). HPV vaccine presents thus some challenging issues for communities, and concerns about the HPV vaccine are a common feature of its introduction.

              The World Health Organization (WHO) recommends that two doses of the currently licensed HPV vaccines be administered to 9–13-year-old girls to prevent infection with two types of human papillomavirus that account for about 70% of cervical cancer cases.

              The full benefits of HPV vaccine in reducing infection and the subsequent risk of cervical cancer will only be appreciated years and even decades after girls have been vaccinated.

              A WHO document provides suggested responses to some common questions that may be raised by patients and parents regarding HPV vaccination in girls4, and a video of WHO explains how the HPV vaccine works: 


              7. Do vaccines cause harmful side effects, illnesses, long-term effects or even death?

                As stated by the World Health Organization (WHO), vaccines are actually very safe, despite implications to the contrary in many anti-vaccine publications. Most vaccine adverse events such as a sore arm or mild fever are minor and temporary. More serious adverse events occur rarely (on the order of one per thousands to one per millions of doses) and some are so rare that the risk cannot be accurately assessed. As for vaccines causing death, again so few deaths can plausibly be attributed to vaccines that it is hard to assess the risk statistically. When, after careful investigation, an event is felt to be a genuine vaccine-related event, it is most frequently found to be a programmatic error, not related to vaccine manufacture.

                In the United States, before the U.S. Advisory Committee on Immunization Practices (ACIP) recommends adding a new vaccine to the immunization schedule, it reviews comprehensive data about vaccine’s safety and efficacy in clinical trials, injuries and deaths caused by the disease the vaccine is designed to combat, as well as the feasibility of adding the new vaccine into the existing schedule, among other factors.

                Many studies have also reversed the suspected link between vaccination against hepatitis B virus and serious adverse events, either in neurological disorders such as multiple sclerosis, or other autoimmune diseases.

                8. What about the presence of aluminium salts in vaccines?

                  Other ingredients are included in a vaccine for specific reasons such as to improve their efficiency. When the safety of a vaccine is evaluated, these ingredients that make up the entire vaccine that is administered are taken into account.

                  In view of the data available to date at the international level, with a use of 90 years and hundreds of millions of doses injected, the French INSERM report considers that the safety of aluminum salts contained in vaccines cannot be questioned.

                  9. Is there a specific link between some vaccinations and autism?

                    According to INSERM5, there is strong scientific evidence that there is no link between measles vaccination - or Measles-Mumps-Rubella (MMR) vaccines - and autism or also inflammatory bowel disease. There is even evidence that the study suggesting a link between MMR vaccination and autism was a scientific fraud. In the USA, the Institute for Vaccine Safety, following the National Academy of Medicine (NAM), also concluded in 2017 that the body of evidence favours rejection of a causal relationship between autism and MMR vaccine and thimerosal-containing vaccines6. Actually, by preventing rubella disease, the MMR vaccine is preventing congenital rubella syndrome and its associated cases of autism. This opinion is based on 13 methodologically sound, controlled epidemiological studies, which explored a possible association between autism and MMR vaccine, thimerosal in vaccines, or simultaneous vaccination with multiple vaccines, in addition to other relevant systematic reviews which together include more than 1.8 million children.

                    5  « Que dit la science à propos des 11 vaccins qui seront obligatoires en France en 2018 pour tous les enfants ? »

                    10. What is the evidence on the safety of immunization during pregnancy?

                      Several challenges exist related to addressing the safety of immunization during pregnancy. The Global Advisory Committee on Vaccine Safety (GACVS) of the WHO established a working group in 2011 to review the evidence available for six groups of vaccine products and address ongoing issues.

                      Regarding vaccine safety for pregnant women and on fetal risk, limited data is available, and liability concerns and methodological issues in assessing vaccine safety during and after pregnancy limit their study through controlled clinical trials7. Meanwhile, vaccination of pregnant women may provide important benefits to the mother and/or her infant. WHO already recommends several vaccinations during pregnancy, and some promising new ones are currently in development, while antenatal immunization against tetanus, influenza and pertussis is recommended and increasingly utilized in many countries.

                      7 Reviewing evidence on the Safety of Immunization During Pregnancy  

                      11. Why are vaccines given in combination?

                        In the United States, children may receive as many as 24 immunizations by their second birthday to protect against 11 diseases and may receive up to five injections during a single doctor’s visit. In order to reduce the number of shots a child receives in a doctor’s visit, some vaccines are offered as combination vaccines. The recommended vaccines have been shown to be as effective in combination as they are individually.

                        The prerequisite for the provision of a combined vaccine is to demonstrate:

                        • That the immune response obtained for each of the valences is not lower than that observed when the different valences are administered separately;
                        • That adverse effects are not more common with the combined form than during the separate (and concomitant) administration of the different vaccines.
                        • That the recommended vaccines have been shown to be as effective in combination as they are individually.

                        In France, a recent update (2018) of the law imposes now 11 vaccines to the young children.

                        12. Does multiple vaccination represent an individual health risk?

                          Sometimes, certain combinations of vaccines given together can cause fever, and occasionally febrile seizures; these are temporary and do not cause any lasting damage. But the arguments that combined vaccines could cause "immune system depletion" are not based on any scientific basis. Scientific data show that getting several vaccines at the same time does not cause any chronic health problems. A number of studies have indeed been done to look at the effects of giving various combinations of vaccines, and when every new vaccine is licensed, it has been tested along with the vaccines already recommended for a particular aged child.

                          According to a report of INSERM (France), the efficacy and safety of combined measles, rubella and mumps vaccines are similar to those of non-combined presentations. Indeed, the stimulation of the immune system induced by multiple vaccines - even “hexavalent” – appears in fact negligible compared to its capacity of response to daily environmental stimulation. The argument of age sometimes invoked has no support since, from birth, infants are in contact with large numbers of antigens.

                          A substantial literature reviewed in the U.S. by the formerly named Institute of Medicine Studies, exists on individual vaccines regarding adverse effects, but few studies have focused on elements of or the recommended childhood immunization schedule as a whole8. Upon reviewing in 2013 stakeholder concerns and scientific literature regarding the entire childhood immunization schedule9 through vaccination, the Committee of the National Academy of Medicine finds no evidence that the schedule is unsafe. The Committee’s review did not reveal any evidence suggesting that the U.S. childhood immunization schedule is linked to autoimmune diseases, asthma, hypersensitivity, seizures, child developmental disorders, learning or developmental disorders, or attention deficit or disruptive disorders. In 2003 already, the U.S. Immunization Safety Review Committee had already reviewed the evidence regarding the hypothesis that multiple immunizations increase the risk for immune dysfunction10 as there were reasonable theories for how vaccines could potentially cause such effects. Regarding more specifically the belief that the Diphtheria-Tetanus-Pertussis DTP vaccine could cause sudden infant death syndrome (SIDS), a number of well-controlled studies conducted during the 1980s allowed the investigators to conclude nearly unanimously, that the number of SIDS deaths temporally associated with this vaccination was within the range expected to occur by chance11. Andfor allergic disease and type 1 diabetes, the Committee found that the epidemiological evidence (i.e., from studies of vaccine-exposed populations and their control groups) favors rejection of a causal relationship between multiple immunizations and increased risk for infections and for type 1 diabetes. In the meantime, the epidemiological evidence regarding risk for allergic disease, particularly asthma, was inadequate to accept or reject a causal relationship.

                          9 The Childhood Immunization Schedule and Safety Stakeholder Concerns, Scientific Evidence, and Future Studies, 2013

                          13. What are the present conclusions of health organisations and authorities about multiple vaccinations?

                            The lack of conclusive evidence linking adverse events to multiple immunizations or other “schedule” exposures suggests that the recommended schedule is safe. According to the U.S. Center for Disease Control (CDC), the scientific data show indeed that getting several vaccines at the same time does not cause any chronic health problems. On this basis, in 2015, both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended again getting all routine childhood vaccines on time.

                            Despite these reassuring available evidence, the Committee nevertheless calls for continued study of the immunization schedule using existing data systems.

                            On the same basis, the World Health Organisation (WHO)12 also considers that these studies have shown that the recommended vaccines are as effective in combination as they are individually, and that such combinations carry no greater risk for adverse side effects. In this context, the CDC and the WHO endorsed answers about a series of misconceptions about vaccination, which are detailed on their websites13. However, in the UK, based upon the available evidence that co-administration of two vaccines can lead to sub-optimal antibody responses to yellow fever, mumps and rubella antigens, and on the different immune mechanisms used by the various vaccines, the Public Health England and the Joint Committee on Vaccination and Immunisation (JCVI) agreed in 2014 that the guidance to either administer the vaccines on the same day or at four week interval period should not be generalised to all live vaccines. They concluded therefore, that intervals between vaccines should be based only upon specific evidence for any interference of those vaccines14.

                            12 WHO - Global Vaccine Safety Six common misconceptions about immunization 
                            14 Joint Committee on Vaccination and Immunisation (JCVI) 2014. Minutes of the February 2014 meeting. [internet]

                            14. What are the risks and responsibilities of not vaccinating a child?

                              The WHO has published a brochure helping to understand the risks and detailing the responsibilities when it is chosen to not vaccinate a child15.

                              In particular, there is responsibility to notify the doctor, local medical facility, ambulance or emergency room personnel that a child has not been fully vaccinated before medical staff have contact with your child or your family members.


                              15. How are vaccines tested before they are authorised for use?

                                In the United States, before a vaccine is recommended for use, the Food and Drug Administration (FDA) makes sure that it works and is safe through years of safety testing16. This includes the testing and evaluation of the vaccine before it is licensed and recommended for use by the Centers for Disease Control and Prevention (CDC). Since the late 1970s, more than 60 studies of vaccine safety have been conducted. During a clinical trial, a vaccine is tested on people who volunteer to get vaccinated. Clinical trials start with 20 to 100 volunteers, but eventually include thousands of volunteers. Since the late 1970s, more than 60 studies of vaccine safety have been conducted.

                                However, the Institute of Medicine (IOM) Committee does not endorse conducting new randomized controlled clinical trials that would compare the health outcomes of unvaccinated children with their fully immunized peers. Although this is the strongest study design type, ethical concerns prohibit this study, as unvaccinated individuals and communities intentionally would be left vulnerable to morbidity and mortality. It considers that the Vaccine Safety Datalink (VSD), a collaborative effort between the CDC and nine managed care organizations that represents the monitoring potentially rare and serious side effects on more than 9 million children and adults, is the best available system for studying the U.S. immunization schedule after vaccines are marketed.


                                16. What are the surveillance systems in place to detect potential problems with existing vaccinations?

                                  To make sure the vaccines meet standards for both quality and safety, the U.S.A. have one of the most advanced systems in the world for tracking vaccine safety. Mechanisms to detect safety signals and provide further confidence that the current childhood immunization schedule is safe include three major surveillance systems:

                                  • The classical U.S. Food and Drug Administration (FDA) procedures;
                                  • The approval of products maintained by the CDC;
                                  • A supplemental vaccine safety monitoring initiative by the FDA.

                                  This monitoring system of vaccine’s safety after these are recommended for infants, children, or adults; together with the company that makes the vaccine tests batches, make sure a vaccine is:

                                  • Potent: It works like it’s supposed to;
                                  • Pure: Certain unwanted ingredients used during production have been removed;
                                  • Sterile: It doesn’t have any outside germs.

                                  The FDA reviews the results of these tests and inspects the factories where the vaccine is made. Each of these systems supplies a different type of data that researchers can analyze. Together, they help to provide a full picture of vaccine safety.

                                  17. Are there some conditions the healthcare provider should be aware of before a vaccination?

                                    It is particularly important to consider whether vaccination should be given or not to children who have weakened immune systems.

                                    This might include being sick or having a history of certain allergic or other adverse reactions to previous vaccinations or vaccine components. For example, if a child is severely allergic to eggs as eggs are used to grow many influenza (flu) vaccines, or to latex as some vaccines are supplied in vials or prefilled syringes that may contain natural rubber latex17


                                    18. Where are vaccinations mandatory and does such obligation increase immunization coverage rates?

                                      As explained by the French INSERM report, since the 19th century, vaccination policies have been resisted by a range of groups opposed to it for philosophical, political, medical, religious or other reasons.

                                      Compulsory vaccination is therefore a difficult policy issue, requiring the authorities to take into account the necessary balance between public health and individual freedom.

                                      In Europe, the choice among decision-makers is divided between the simple recommendation of vaccination and the obligation. In the latter case, it is more or less difficult for countries to obtain exemptions.

                                      The report of the European ASSET project18, in the framework of the 7th Framework Program for Research and Development, concludes that it is impossible to confirm a relationship between the obligation and the immunization coverage rates (polio, measles and pertussis) of children in Europe.

                                      This may suggest that other factors than vaccination policies and parental hesitancy could come into play, such as the ability of health systems to reach all children: for example, free and easy access to vaccination. It should be emphasized that the conclusions of the ASSET project do not take into account the important cultural differences between European countries, particularly in the field of health prevention.

                                      In the U.S.A, there is a difference between federal vaccine policies and state vaccine laws. Federal public health officials at the CDC make national vaccine policy recommendations for children and adults. With the approval of state legislatures, public health officials in state health departments make and enforce vaccine mandates. That is why vaccine laws and legal exemptions to vaccination vary from state to state19.

                                      Main references :

                                      The Childhood Immunization Schedule and Safety Stakeholder Concerns, Scientific Evidence, and Future Studies
                                      World Health Organisation (WHO) Global Vaccine Safety1
                                      Mise au point de l’Inserm Décembre 2017. Que dit la science à propos des 11 vaccins qui seront obligatoires en France en 2018 pour tous les enfants ?

                                      1 Publications of the World Health Organization are available on the WHO website  or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders (at) ).
                                      18 ASSET, Action Plan for Science in Society related issues in Epidemics and Total pandemics - Compulsory Vaccination and Rates of Coverage Immunisation in Europe, 2016 ;

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