Do Vaccine Ingredients Cause Adverse Events?

Conclusion | Why This is an Issue | Epidemiological Evidence | Archives | References


Conclusion

Certain ingredients that are present in some vaccines (other than disease-specific antigens), such as gelatin or neomycin, can very rarely cause severe hypersensitivity reactions (e.g. anaphylaxis) in vaccinees with those specific allergies. In addition, some adjuvants can cause increased rates of local reactions, and alum containing adjuvants can cause nodules at the injection site.
Vaccine ingredients, including the preservative thimerosal, do not cause autism. Ingredients in vaccines currently routinely recommended to the general population in the U.S. have not been shown to cause any other adverse events.

Why This is an Issue

As part of the Food and Drug Administration (FDA) Modernization Act of 1997, the FDA conducted an analysis on exposure to mercury in children. This led them to examine the risk of thimerosal, an ethyl-mercury containing preservative that was present in some vaccines at the time. The FDA risk assessment revealed no evidence of harm caused by the doses of thimerosal in vaccines other than local hypersensitivity reactions [1]. However, the exposure exceeded the United States Environmental Protection Agency (EPA) guidelines for methylmercury exposure; there were no available guidelines for ethyl-mercury, which is now known to have a shorter half-life than methylmercury. Long term follow-up of children to evaluate the risk of mild neurologic effects from ethyl-mercury had not been conducted at that time. Because of the uncertainty in the risk assessment, as a precautionary measure thimerosal was removed as a preservative from most vaccines administered to children (small amounts of thimerosal are still present in multi-dose vials of influenza vaccine).

Around this time, concern about autism and MMR vaccine had also begun to increase (see the Do Vaccines Cause Autism? summary for more details).  As evidence mounted that MMR vaccine was not associated with autism, some autism interest groups shifted their hypothesis from MMR vaccine to the belief that thimerosal was causing autism in children. This theory was based upon observed similarities in some features of autism spectrum disorder (ASD) and mercury poisoning [2]. The plausibility of this suspected association was refuted by neurologists and several large studies have documented that thimerosal was not associated with an increased risk of autism spectrum disorder [3]. More information is available on the website of the Centers for Disease Control and Prevention (CDC) at http://www.cdc.gov/vaccinesafety/concerns/thimerosal.

Other vaccine ingredients including preservatives, adjuvants, or manufacturing residuals, can sound scary to the general public, especially when they are poorly understood. This has caused some understandable, albeit unfounded, concerns regarding the safety of these ingredients. Examples of this are aluminum and formaldehyde, which are known toxins for humans when consumed in large quantities. However, one must always keep the dosage in mind, as a great many things can be toxic with a high enough exposure. In the case of these vaccine ingredients, they present no danger in the miniscule quantities in which they are used in vaccines (which is typically much less than is found naturally in the body, common food or the environment), and serve only to stabilize the vaccine or enhance the immune response [4]. More information is available on the FDA website at: http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm187810.htm.

Epidemiological Evidence

Epidemiological evidence: Five methodologically sound, controlled epidemiological studies found no association between autism spectrum disorder (ASD) and thimerosal in vaccines [5-9], as well as the relevant systematic reviews [10, 11] and a meta-analysis [12]. The Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), concluded that the body of evidence favors rejection of a causal relationship between autism and thimerosal-containing vaccines [13]. See the Do Vaccines Cause Autism? summary for more details.

A few studies have reported an association between vaccines containing aluminum adjuvants and persistent nodules at the injection site, at an estimated rate of 0.03-0.83% [14-17]. Two studies examining infant exposure to aluminum from both diet and vaccines that include aluminum adjuvants concluded that the levels of aluminum in vaccines are well below the calculated safe body burden [18, 19].

A review of data on substances sometimes found in certain vaccines in very small quantities, such as thimerosal, aluminum, gelatin, human serum albumin, formaldehyde, antibiotics, egg proteins, and yeast proteins, found no evidence of harm other than rare instances of hypersensitivity reactions such as anaphylaxis in those with severe allergies to either gelatin or egg proteins [4]. See the Do Vaccines Cause Anaphylaxis? summary for more details.

References

1. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics 2001;107:1147-54.
2. Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of mercury poisoning. Medical hypotheses 2001;56:462-71.
3. Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics 2003;111:674-9.
4. Offit PA, Jew RK. Addressing parents' concerns: do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 2003;112:1394-7.
5. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. Jama 2003;290:1763-6.
6. Verstraeten T, Davis RL, DeStefano F, et al. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics 2003;112:1039-48.
7. Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association. Pediatrics 2004;114:584-91.
8. Croen LA, Matevia M, Yoshida CK, Grether JK. Maternal Rh D status, anti-D immune globulin exposure during pregnancy, and risk of autism spectrum disorders. Am J Obstet Gynecol 2008;199:234.e1-6.
9. Price CS, Thompson WW, Goodson B, et al. Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics 2010;126:656-64.
10. Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics 2004;114:793-804.
11. Schultz ST. Does thimerosal or other mercury exposure increase the risk for autism? A review of current literature. Acta neurobiologiae experimentalis 2010;70:187-95.
12. Taylor LE, Swerdfeger AL, Eslick GD. Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine 2014;32:3623-9.
13. Institute of Medicine Immunization Safety Review C. The National Academies Collection: Reports funded by National Institutes of Health. Immunization Safety Review: Vaccines and Autism. Washington (DC): National Academies Press (US); 2004.
14. Baylor NW, Egan W, Richman P. Aluminum salts in vaccines--US perspective. Vaccine 2002;20 Suppl 3:S18-23.
15. Bergfors E, Hermansson G, Nystrom Kronander U, Falk L, Valter L, Trollfors B. How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study. European journal of pediatrics 2014;173:1297-307.
16. Bergfors E, Trollfors B, Inerot A. Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine 2003;22:64-9.
17. Netterlid E, Bruze M, Hindsen M, Isaksson M, Olin P. Persistent itching nodules after the fourth dose of diphtheria-tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium. Vaccine 2004;22:3698-706.
18. Keith LS, Jones DE, Chou CH. Aluminum toxicokinetics regarding infant diet and vaccinations. Vaccine 2002;20 Suppl 3:S13-7.
19. Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine 2011;29:9538-43.