Conclusion
Influenza vaccines do not cause multiple sclerosis (MS).Other vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause MS.
Epidemiological Evidence
Most studies described in the 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), found no association between vaccination and MS, whether assessing onset 1-5 or relapse 6,7 in adults, or onset 1,8 or relapse 9 in children; however, these studies did not provide convincing evidence due to a lack of validity and precision 10. Studies published since the 2012 IOM report focusing on the pandemic H1N1 influenza vaccine Pandremix 11-13, quadrivalent HPV vaccine (Gardasil®) 14-17 and hepatitis B vaccine 15 have also found no association with MS. A large German case-control study suggests that vaccination may even have a protective effect against MS 18.
A white paper on influenza vaccine safety published in 2015 concluded that while each individual study had relatively low power, as a group they provide consistent evidence against a causal association between influenza vaccine in adults and MS onset or relapse; although the data are more limited in children, there is no signal to indicate concern 19. A 2016 systematic review found no increase in risk of development of MS after vaccination against hepatitis B, HPV, influenza, MMR, tetanus, diphtheria, polio, smallpox, or BCG vaccines 20. A 2017 literature review found no increase in risk of onset or relapse of MS after vaccination 21. A 2018 systematic review found no association between hepatitis B vaccines and MS or central demyelination 22. A 2020 systematic review and meta-analysis found no association between HPV vaccines and many autoimmune or other rare diseases (including MS) 23. A 2021 Cochrane review determined that no evidence supports an association between MMR vaccination and MS 24. A 2021 systematic review and meta-analysis found no association between hepatitis B vaccines and MS 25.
Proposed Biological Mechanism
Hypersensitivity reactions triggered by autoimmunity, genetics or environmental factors such as viral infection are often incriminated in the destruction of the host’s myelin basic protein (MBP) and other antigens 26. Similarities in features of MS and other demyelinating disorders have been described and some subjects with the diagnosis of Acute Disseminated Encephalomyelitis (ADEM) have had recurrences and progressed to MS 27,28. One possible mechanism is molecular mimicry, which refers to the possibility that similar epitopes shared between self-peptides and foreign peptides (introduced via infection or immunization) inadvertently cause the activation of autoreactive T or B cells, leading to autoimmunity.
Of the many vaccines assessed for a possible association with MS, the hepatitis B vaccine has captured the most interest, because molecular mimicry has been demonstrated in rabbits between hepatitis B viral polymerase and the part of the MBP that leads to encephalitis 29. This suggests that infection with a virus showing similarities with MBP regions associated with the development of encephalitis could induce MS through molecular mimicry. However, the IOM concluded that there was no mechanistic evidence for an association between vaccination and MS, as the publications reviewed provided no evidence beyond a temporal association 10.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
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