Vaccine Safety: Immune System and Health

Some concerns about vaccine safety relate to how vaccines interact with the immune system (e.g., too many vaccines) or even how the immune system functions in different situations (e.g., natural infection versus immunization). While it is fair to consider these concerns, it is important to understand them in the context of how the immune system works.

On this page

More information about the following can be found on this page:

  • Natural infection versus immunization
    • Is natural infection better than immunization? (Includes list of vaccines that cause greater immune responses than natural infection)
    • Are vaccines natural?
    • Are nosodes viable alternatives to vaccination?
  • Impact of vaccines on the immune system
    • Do vaccines overwhelm the immune system? (“Too many vaccines?”)
    • Number of immunogenic proteins in vaccines (Includes infographic)
    • Do vaccines weaken the immune system?
    • Can sick children receive vaccines?
    • Are children too young to receive vaccines?
    • Can children manage so many vaccines?
  • Vaccine viruses: Impact on other people’s immune systems
    • Viral shedding after receipt of live viral vaccines
  • References

For more information about the immune system and how it works, visit the website section called, “Human Immune System.”

Natural infection versus immunization

Is natural infection better than immunization?

It is true that natural infection almost always causes better immunity than vaccines. Whereas immunity from disease often follows a single natural infection, immunity from vaccines usually occurs only after several doses. However, the difference between vaccination and natural infection is the price paid for immunity:

  • The price paid for immunity after natural infection might be pneumonia from chickenpox, intellectual disability from Haemophilus influenzae type b (Hib), pneumonia from pneumococcus, birth defects from rubella, liver cancer from hepatitis B virus, or death from measles.
  • Immunization with vaccines, like natural infections, typically induces long-lived immunity. But unlike natural infection, immunization does not extract such a high price for immunity; that is, immunization does not cause pneumonia, intellectual disability, birth defects, cancer or death.

If you could see the world from the perspective of your immune system, you would realize that where the virus or bacteria comes from is irrelevant. Your immune system “sees” something that is foreign, attacks it, disables it and then adds information to the memory bank, so your body can react more quickly the next time that same foreign invader arrives.

The differences between a vaccine and getting the disease naturally are the dose and the known time of exposure:

  • Dose — When someone is exposed to viruses or bacteria naturally, the dose is often larger, so the immune response that develops will typically be greater — as will the symptoms. However, when scientists are designing vaccines, they determine the smallest amount of virus or bacteria needed to generate a protective immunologic response. In this situation, more is not necessarily better.
  • Time of exposure — Most of the time, we do not know when we are exposed to viruses and bacteria; however, when we get a vaccine, we know about the exposure. In essence, we are controlling exposure to the viruses or bacteria that the vaccines protect against because we know when and where they occur. In contrast, and more typical of the norm, we don’t know what viruses or bacteria we are exposed to from the trip to get the vaccine — the door knob, the office, the books in the waiting room, or the toddler at the restaurant we go to after the office visit. Luckily, most of these exposures do not result in infections that our immune system is unable to control.

Of interest, a few vaccines induce a better immune response than natural infection:

  • Human papillomavirus (HPV) vaccine — The high purity of the specific protein in the vaccine leads to a better immune response than natural infection.
  • Tetanus vaccine — The toxin made by tetanus is so potent that the amount that causes disease is actually lower than the amount that induces a long-lasting immune response. This is why people with tetanus disease are still recommended to get the vaccine.
  • Haemophilus influenzae type b (Hib) vaccine — Children less than 2 years old do not typically make a good response to the complex sugar coating (polysaccharide) on the surface of Hib that causes disease; however, the vaccine links this polysaccharide to a helper protein that creates a better immune response than would occur naturally. Therefore, children less than 2 years old who get Hib are still recommended to get the vaccine.
  • Pneumococcal vaccine — This vaccine works the same way as the Hib vaccine to create a better immune response than natural infection.

So, in summary, vaccines afford us protection with lesser quantities of virus or bacteria and the control of scheduling the exposure.

Listen to Dr. Offit explain natural infection and vaccination by watching this short video, part of the Talking About Vaccines with Dr. Paul Offit video series.

Are vaccines natural?

Many of today’s consumers crave organic, all-natural, or free-range products. Willing to pay more and drive further to get these products, they believe they are keeping their families healthy. Some of these same people forego vaccines claiming that they are not natural.

What is “natural”?

According to the Merriam-Webster dictionary, natural means “being in accordance with or determined by nature.” Viruses and bacteria are natural; diseases caused by them are natural.

Because vaccines are made using parts of the viruses and bacteria that cause disease, the ingredient that is the active component of the vaccine that induces immunity is natural. However, critics point to other ingredients in vaccines or the route of administration as being unnatural.

Vaccine ingredients

“Green our vaccines” is a mantra of those who believe that the ingredients in vaccines are harmful and unnatural. However, vaccine vials contain well-characterized ingredients in known quantities.

Vaccines contain three types of ingredients other than the virus or bacterium of interest:

  • Adjuvants enhance the immune response, typically allowing for lesser quantities of the viral or bacterial components to be used in the vaccine. Aluminum is an example.
  • Stabilizers protect the proteins in the vaccine from being degraded during manufacture and transport. Gelatin is an example.
  • Preservatives keep the vaccine from becoming contaminated. Thimerosal, a mercury-containing preservative, is perhaps the most well-known, although it has been removed from all childhood vaccines, except some multi-dose vials of influenza vaccine given to older infants and children.
  • For in-depth discussions, consult the following resources:
    • “Vaccine Ingredients: What You Should Know” - English [PDF, 817KB]; Spanish [PDF, 832KB]
    • “Aluminum: What You Should Know” - English [PDF, 296KB]; Spanish [PDF, 333KB]; Japanese [PDF, 948KB]
    • “Is the Aluminum in Vaccines Safe?” – Video
    • “Thimerosal: What You Should Know” - English [PDF, 193KB]; Spanish [PDF, 209KB]
    • “Is There Mercury in Vaccines?” – Video

Some wonder about the quantity of different additives in vaccines or the cumulative effect from several vaccines. This is a valid concern; in fact, the Swiss chemist Paracelsus coined the phrase, “the dose makes the poison.” However, the good news is that the quantities of ingredients in vaccines are determined to be the lowest amounts necessary and when vaccines are given together, they must be studied together. So, the quantities of ingredients in vaccines have been determined to be safe.

Route of administration

Viruses and bacteria typically enter the body through our nose or mouth. With the exception of the oral rotavirus vaccine and the intranasal flu vaccine, most vaccines are given as a shot. While at first glance the injections appear to be different or “unnatural,” they are not when you consider what happens in each case.

When viruses or bacteria enter the body through the nose or mouth, they are detected by cells of the immune system that line the surfaces of these areas of entry. These “foreign invaders” are ingested by immune cells and processed in lymph nodes in the region of the infection. The immune response has two aspects, local and systemic. The immune cells are produced near the site of the infection, but they are dispersed throughout the body via the bloodstream. After the infection has been resolved, a small number of immune memory cells continue circulating to monitor for future infections. Because these memory responses are specific, subsequent exposures to the same virus or bacterium generate a quicker and stronger immune response that completely prevents or significantly lessens the effects and duration of illness.

Vaccines are no different. Although common belief is that vaccines are injected directly into the bloodstream, they are actually administered into muscle or the layer of skin below the dermis where immune cells reside and circulate, as occurs following natural infection.

In conclusion

The active ingredients in vaccines are the parts of the viruses or bacteria to which we make an immune response. The additional ingredients are determined to be the lowest plausible quantities and are studied as part of the vaccine during safety testing. The immune system responds in the same way it would to the virus or bacteria following unexpected introduction. So, while not natural in that they are given at specified times, vaccines offer a controlled way to protect ourselves from the viruses or bacteria that cause illness.

Are nosodes viable alternatives to vaccination?

The short answer to this question is no. Nosodes are products taken from the body, diluted extensively (often to the point that no product of interest remains), and used as a homeopathic treatment.

Let’s take the example of a nosode to prevent human papillomavirus (HPV). The nosode is made by first taking fluid from the cervix of a woman infected with HPV. The fluid is then diluted to the point that no HPV is present. Therefore, a nosode is composed only of the fluid that was used to dilute the virus. For this reason, an HPV nosode cannot possibly prevent HPV infection. 

A nosode vaccine is made using the concept of homeopathy, which was first introduced by Dr. Samuel Hahnemann. Proponents of homeopathy believe that while, in this case, HPV is no longer present in the nosode, the solution maintains a “memory” of the original agent that protects the patient from subsequent infection. No evidence supports this notion. And, quite frankly, it’s a good thing that the original HPV is no longer present. Otherwise, the recipient would be at risk of catching the virus.

Real vaccines, on the other hand (like the HPV vaccine), are made with known, measurable quantities of killed pathogens or individual pieces of them, such as proteins or inactivated toxins. Likewise, measurable immune responses are generated. In contrast, nosodes are made from solutions that have been randomly diluted (different providers dilute the materials differently) such that no measurable material remains. Because no infectious material remains, measurable immune responses are not generated.

In July 2015, the Canadian Minister of Health required changes to labelling of nosodes. Beginning in January 2016, any nosodes had to include the following statement: “This product is neither a vaccine nor an alternative to vaccination. This product has not been proven to prevent infection. Health Canada does not recommend its use in children and advises that your child receive all routine vaccinations.”


Impact of vaccines on the immune system

Do vaccines overwhelm the immune system? (Too many vaccines?)

Studies on the diversity of antibody specificities indicate that the immune system has the capacity to respond to extremely large numbers of immunologically distinct regions of viruses and bacteria. Current data suggest that the theoretical capacity determined by the genes that make different antibodies would allow for as many as 109-1011 different kinds of antibodies (i.e., 1 billion to 100 billion). But this theoretical capacity is limited by the number of circulating antibody-producing cells (B cells or lymphocytes) and the likely redundancy of antibodies generated by one individual.

A more practical way to determine the diversity of the immune response would be to estimate the number of vaccines to which a child could respond at one time. Assuming the quantities of antibodies likely generated by an individual in 1 ml of blood (one-fifth of a teaspoon) during seven days after exposure to a vaccine, and the number of different specificities of those antibodies, then each infant would have the capacity to respond to about 10,000 vaccines at any one time. Using this estimate, one would predict that if 11 vaccines were given to infants at one time, then about 0.1 percent of the immune system would be "used up."

However, because B cells and other lymphocytes are constantly replenished, a vaccine never really "uses up" a fraction of the immune system. For example, the immune system has the ability to replenish about 2 billion lymphocytes each day. This replacement activity illustrates the enormous capacity of the immune system to generate lymphocytes as needed.

Parents may also take comfort in knowing that children are exposed to fewer immunologic components (like proteins and sugars [polysaccharides]) in vaccines today than in the past. The table below summarizes the number of proteins and polysaccharides contained in routinely recommended vaccines administered during the past 100 years. Although we now give children more vaccines, the actual number of immunologic components in vaccines has declined.

DO VACCINES OVERWHELM THE IMMUNE SYSTEM? To view the full size infographic, click this photo or the link below. Whereas previously one vaccine, smallpox, contained about 200 proteins, now the 14* routinely recommended vaccines contain about 160 immunologic components (i.e., proteins or polysaccharides). Two factors account for this decline: first, the worldwide eradication of smallpox obviated the need for that vaccine, and second, advances in protein chemistry have resulted in vaccines containing fewer antigens (e.g., replacement of whole-cell with acellular pertussis vaccine). Check this infographic and the table below it for more information:

Download image [PDF, 121KB]

*Infants and young children receive vaccines to prevent 14 different diseases; some are given in combination.

Number of immunogenic proteins or sugars (polysaccharides) contained in vaccines over the past 100 years

1900 | Totals: ~200

  • Smallpox - Proteins: ~200

1960 | Totals: ~3,217

  • Smallpox - Proteins: ~200
  • Diphtheria - Proteins: 1
  • Tetanus - Proteins: 1
  • Whole cell Pertussis - Proteins/Sugars: ~3,000
  • Polio - Proteins: 15

1980 | Totals: ~3,041

  • Diphtheria - Proteins: 1
  • Tetanus - Proteins: 1
  • Whole cell Pertussis - Proteins/Sugars: ~3,000
  • Polio - Proteins: 15
  • Measles - Proteins: 10
  • Mumps - Proteins: 9
  • Rubella - Proteins: 5

2000 | Totals: 134-137

  • Diphtheria - Proteins: 1
  • Tetanus - Proteins: 1
  • Acellular pertussis Proteins: 2-5
  • Polio - Proteins: 15
  • Measles - Proteins: 10
  • Mumps - Proteins: 9
  • Rubella - Proteins: 5
  • Hib - Proteins: 2
  • Varicella - Proteins: 69
  • Pneumococcus - Proteins/Sugars: 8
  • Hepatitis B Proteins: 1
  • Influenza - Proteins: 11

2021 | Totals: 149-157

  • Diphtheria - Proteins: 1
  • Tetanus - Proteins: 1
  • Acellular pertussis Proteins: 2-5
  • Polio - Proteins: 15
  • Measles - Proteins: 10
  • Mumps - Proteins: 9
  • Rubella - Proteins: 5
  • Hib - Proteins: 2
  • Varicella - Proteins: 69
  • Pneumococcus - Proteins/Sugars: 8
  • Hepatitis B Proteins: 1
  • Influenza - Proteins: 11
  • Rotavirus - Proteins: 11-16
  • Hepatitis A – Proteins: 4 

Adapted from: Offit PA, et al. Addressing parents' concerns: Do vaccines weaken or overwhelm the infant's immune system? Pediatrics 2002;109:124-129.

Learn more about concerns surrounding the number of vaccines by watching this short video, part of the Talking About Vaccines with Dr. Paul Offit video series.

Do vaccines weaken the immune system?

Vaccinated children are not at greater risk of other infections (infections not prevented by the vaccines) than unvaccinated children. On the contrary, in Germany, a study of 496 vaccinated and unvaccinated children found that children who received immunizations against diphtheria, pertussis, tetanusHaemophilus influenzae type b (Hib) and polio within the first three months of life had fewer infections with vaccine-related and unrelated pathogens than the non-vaccinated group.

Bacterial and viral infections, on the other hand, often predispose children and adults to severe, invasive infections with other pathogens. For example, children with pneumococcal pneumonia are more likely to have had a recent influenza infection than other children. Similarly, varicella infection increases susceptibility to the 'flesh-eating bacteria (i.e., group A strep).

Can sick children receive vaccines?

Some parents might be concerned that children with acute illnesses are less likely to respond to vaccines or are more likely to develop severe reactions to vaccines than are healthy children. Alternatively, some parents might believe that children who are ill shouldn't further burden an immune system already committed to fighting an infection. However, vaccine-specific antibody responses and rates of vaccine-associated adverse reactions of children with mild or moderate illnesses are comparable to those of healthy children. For example, the presence of upper respiratory tract infections, ear infections, fever, skin infections or diarrhea does not affect the level of protective antibodies induced by immunization.

Data on the capacity of vaccines to induce protective immune responses in children with severe infections (such as those with bacterial pneumonia or meningitis) are lacking. Although a delay in vaccines is recommended for children with severe illnesses until the symptoms of illness resolve, this recommendation is not based on the likelihood that the child will have an inadequate immune response to the vaccine. Rather, the reason for deferring immunization is to avoid superimposing a reaction to the vaccine on the underlying illness or to mistakenly attribute a manifestation of the underlying illness to the vaccine.

Are children too young to receive vaccines?

No. If children are not too young to be permanently harmed or killed by viruses or bacteria, they aren't too young to be vaccinated to prevent those diseases. Because the diseases that vaccines prevent often occur in very young infants, the only way to prevent them is to give vaccines soon after birth. Fortunately, infants given vaccines in the first few months of life are quite capable of making a protective immune response.

Find out more about the development of the immune system.

Watch a video clip about whether children are too young to get vaccines.

Can children manage so many vaccines?

The mother's womb is essentially a sterile environment. The fluid surrounding the baby is free from bacteria. However, within minutes of leaving the womb, the child must confront thousands of bacteria. By the end of the first week of life, the child's skin, nose, throat and intestines are covered with tens of thousands of different bacteria.

Fortunately, from the moment of birth, infants begin to develop an active immune response to these bacteria — an immune response that prevents these bacteria from entering the bloodstream and causing harm.

The vaccines that children receive in the first two years of life are just a drop in the ocean when compared with the tens of thousands of environmental challenges that babies successfully manage every day.

Watch a video clip about getting multiple vaccines at one time.

Vaccine viruses: Impact on other people’s immune systems

Viral shedding after receipt of live viral vaccines

When we get sick with viruses, we transmit them to others through a variety of routes, such as through coughing and sneezing when the infections are in our respiratory systems, but also through ingestion, particularly if the virus reproduces in our intestinal tract and is present in feces. This spread of virus from one person to another is called viral shedding.

Because some vaccines contain live viruses (e.g., chickenpox, rotavirus, measles, mumps, rubella, and polio [a version no longer used in the U.S.], people wonder whether the viruses from vaccines are shed and can, therefore, make other people sick. Scientists wondered, too, so when they made these vaccines, they also studied viral shedding.

In most cases, even if the vaccine virus is shed, it is not likely to make other people sick for two reasons. First, the vaccine virus reproduces much less than one from the environment because it has been weakened to make the vaccine. As a result, less virus is shed. Second, even if another person is exposed to vaccine virus that is shed following the vaccination of someone else, the weaker vaccine virus is unlikely to make the second person ill for the same reason it does not make the first person ill – it has been designed to provide immunity without causing symptoms. In fact, this characteristic was important in the fight to eradicate polio. When people got the oral polio vaccine, they would shed the vaccine virus. As a result, the vaccine virus would circulate in the community, and others who were not vaccinated sometimes became immune. This is called contact immunity.

Sometimes, however, live, weakened viral vaccines can be of concern. For example, in the case of someone who is immune compromised, live viral vaccines are typically not recommended because their immune systems may not be able to stop even the weakened viral infection. The result could be a long-term infection. For this reason, sometimes people wonder whether they, or infants and children in the home of someone who is immune compromised, can get live, weakened viral vaccines. In most cases, the answer is yes. The oral polio vaccine was an exception, however, because it was shed in quantities sufficient to spread to others, it was recommended that those living in the home of someone who was severely immune compromised not get the oral polio vaccine. Other live viral vaccines, on the other hand, can be given in the home of someone who is immune compromised.

See this downloadable file for more information:


Glanz JM, Newcomer SR, Daley MF, DeStefano F, et al. Association between estimated cumulative vaccine antigen exposure through the first 23 months of life and non-vaccine-targeted infections from 24 through 47 months of ageJAMA 2018;319(9):906-913.
The authors determined the relationship between the number of vaccines given in the first two years of life and the occurrence of non-vaccine targeted infections between two and four years of age. They found no difference in either the cumulative number of antigens or the number of antigens received in a single day in children who developed non-vaccine targeted infections.

Sherrid AM, Ruck CE, Sutherland D, et al. Lack of broad functional differences in immunity in fully vaccinated vs. unvaccinated childrenPediatr Res 2017;81(4):601-608.
The authors assessed the immune response to general, non-vaccine specific stimuli in fully vaccinated and entirely unvaccinated children between 3 and 5 years of age. They found that standard childhood vaccines did not cause long-lasting, gross alterations of the immune system.

DeStefano F, Price CS, Weintraub ES. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autismJ Pediatr 2013;163:561-567.
The authors evaluated the relationship between the total cumulative vaccine-specific antigen exposure or maximum exposure on a single day and the development of autism spectrum disorder (ASD), autistic disorder (AD) or ASD with regression. They found no association between antigen exposure from vaccines during the first two years of life and the risk of developing ASD, AD, or ASD with regression.

Iqbal S, Barile JP, Thompson WW, DeStefano F. Number of antigens in early childhood vaccines and neuropsychological outcomes at age 7-10 yearsPharmacoepidemiol Drug Saf 2013;22:1263-1270.
The authors compared neuropsychological outcomes in more than 1,000 children aged 7-10 years with the number of vaccine-specific antigens to which they were exposed during the first 24 months of life. They found no correlation between the number of vaccine-specific antigens received and adverse neuropsychological outcomes.

Smith MJ and Woods CR. On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomesPediatrics 2010;125;1134-1141.
The authors compared long-term neuropsychological outcomes in children who received vaccines on time with those with delayed or incomplete vaccination during infancy. Timely vaccination was not associated with adverse neuropsychological outcomes 7 to 10 years later. The authors concluded that there was no benefit in delaying immunizations during the first year of life.

Hviid A, Wohlfahrt J, Stellfeld M, et al.  Childhood vaccination and nontargeted infectious disease hospitalizationJAMA 2005;294(6):699-705.
The authors evaluated the relationship between routinely administered childhood vaccines and the occurrence of non-targeted infectious diseases in more than 800,000 children. They found that neither the number of vaccines nor the receipt of multiple-antigen vaccines increased the risk of hospitalizations caused by non-targeted infectious diseases.

Offit PA, Quarles J, Gerber MA, et al.  Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant’s immune system? Pediatrics 2002;109(1):124-129.
Given the number of antibody-generating B cells in the circulation, the number of vaccine-specific antigens to which infants are exposed during the first few years of life, and the quantity of antibodies necessary to react to each antigen, the authors estimated that infants have the theoretical capacity to respond to at least 10,000 vaccines at one time. The authors also showed that the number of immunological components in current vaccines is actually less than the one vaccine (smallpox) that children received 100 years ago.

Reviewed by Paul A. Offit, MD on March 11, 2021

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.