Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.
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Centers for Disease Control and Prevention Surveillance for acute viral hepatitis–United States, 2006 MMWR Surveillance Summaries March 21, 2008. [online],
Toplak, N. et al. Autoimmune response following annual influenza vaccination in 92 apparently healthy adults. Autoimmun. Rev. 8, 134–138 (2008).
Agmon-Levin, N., Kivity, S. & Shoenfeld, Y. Transverse myelitis and vaccines: a multiple analysis. Lupus (in press).
Lasky, T. et al. The Guillain–Barre syndrome and the 1992–1993 and 1993–1994 influenza vaccines. N. Engl. J. Med. 339, 1797–1802 (1998).
Classen, J. B. & Classen, D. C. Clustering of cases of insulin dependent diabetes (IDDM) occurring three years after hemophilus influenza B (HiB) immunization support causal relationship between immunization and IDDM. Autoimmunity 35, 247–253 (2002).
Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré syndrome among recipients of Menactra® meningococcal conjugate vaccine, United States, June 2005, September 2006. MMWR 55, 1120–1124 (2006).
Ascherio, A. et al. Hepatitis B vaccination and the risk of multiple sclerosis. N. Engl. J. Med. 344, 327–332 (2001).
Mikaeloff, Y., Caridade, G., Suissa, S. & Tardieu, M. Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood. Neurology 72, 873–880 (2009).
Bonhoeffer, J. et al. Standardized case definitions of adverse events following immunization (AEFI). Vaccine 22, 547–550 (2004).
WHO, Global advisory committee on vaccine safety. Causality assessment of adverse events following immunization. Wkly Epidemiol. Rec. 76, 85–89 (2001).
Hogenesch, H., Azcona-Olivera, J., Scott-Moncrieff, C., Snyder, P. W. & Glickman, L. T. Vaccines induced autoimmunity in dogs. Adv. Vet. Med. 41, 733–747 (1999).
Classen, J. B. The timing of immunization affects the development of diabetes in rodents. Autoimmunity 24, 137–145 (1996).
Koppang, E. O. et al. Vaccination-induced systemic autoimmunity in farmed Atlantic salmon. J. Immunol. 181, 4807–4814 (2008).
Albert, L. J. & Inman, R. D. Molecular mimicry and autoimmunity. N. Engl. J. Med. 341, 2068–2074 (1999).
Arbuckle, M. R. et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533 (2003).
Edwards, C. J. et al. The presence of anticardiolipin antibodies in adults may be influenced by infections in infancy. QJM 101, 41–47 (2008).
Ram, M. & Shoenfeld, Y. Hepatitis B: infection, vaccination and autoimmunity. Isr. Med. Assoc. J. 10, 61–64 (2008).
Kivity, S., Agmon-Levin, N., Blank, M. & Shoenfeld, Y. Infectious and autoimmunity—friends or foe? Trends Immunol. 30, 409–414 (2009).
Israeli, E., Agmon-Levin, N., Blank, M. & Shoenfeld, Y. Adjuvants and autoimmunity. Lupus (in press).
Gavin, A. et al. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science 314, 1936–1938 (2006).
Kool, M. et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J. Exp. Med. 205, 869–882 (2008).
Satoh, M. & Reeves, W. H. Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J. Exp. Med. 180, 2341–2346 (1994).
Gherardi, R. K. & Authier, F. J. Aluminum inclusion macrophagic myofasciitis: a recently identified condition. Immunol. Allergy Clin. North Am. 23, 699–712 (2003).
Petrik, M. S., Wong, M. C., Tabata, R. C., Garry, R. F. & Shaw, C. A. Aluminum adjuvant linked to gulf war illness induces motor neuron death in mice. Neuromolecular Med. 9, 83–100 (2007).
Asa, P. B., Cao, Y. & Garry, R. F. Antibodies to squalene in Gulf War syndrome. Exp. Mol. Pathol. 68, 55–64 (2000).
Yu, O. et al. Hepatitis B vaccine and risk of autoimmune thyroid disease: a Vaccine Safety Datalink study. Pharmacoepidemiol. Drug Saf. 16, 736–745 (2007).
Shoenfeld, Y. et al. The mosaic of autoimmunity: genetic factors involved in autoimmune diseases 2008. Isr. Med. Assoc. J. 10, 3–7 (2008).
Gluck, T. & Muller-Landner, U. Vaccination in patients with chronic rheumatic or autoimmune diseases. Clin. Infect. Dis. 46, 1459–1465 (2008).
Conti, F., Rezai, S. & Valesini, G. Vaccination and autoimmune rheumatic diseases. Autoimmun. Rev. 8, 124–128 (2008).
Stassen, P. M., Sanders, J. S., Kallenberg, C. G. & Stegeman, C. A. Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol. Dial. Transplant. 23, 654–658 (2008).
N. Agmon-Levin and Z. Paz have contributed equally to the preparation of this manuscript.
Y. Shoenfeld has acted as a consultant for the no-fault U.S. National Vaccine Injury Compensation Program. The other authors declare no competing interests.
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Agmon-Levin, N., Paz, Z., Israeli, E. et al. Vaccines and autoimmunity. Nat Rev Rheumatol 5, 648–652 (2009). https://doi.org/10.1038/nrrheum.2009.196
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