Journal of Neurology

, Volume 264, Issue 6, pp 1035–1050 | Cite as

Vaccines and multiple sclerosis: a systematic review

  • Mia Topsøe Mailand
  • Jette Lautrup FrederiksenEmail author


Vaccinations are often the most effective tool against some disease known to mankind. This study offers a literature review on the role of vaccines regarding the risk of developing multiple sclerosis (MS) and MS relapse. The method used in this study is a systematic literature review on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse was found for influenza. Further research is needed for the potential therapeutic use of the BCG vaccine in patients in risk of developing MS and for the preventive potential of the tetanus and diphtheria vaccine.


Multiple sclerosis Vaccination Immunization 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Denis F, Levy-Bruhl D (2006) Mass vaccination against hepatitis B: the French example. Curr Top Microbiol Immunol 304:115–129PubMedGoogle Scholar
  2. 2.
    Williamson EM, Berger JR (2015) Infection risk in patients on multiple sclerosis therapeutics. CNS Drugs 29(3):229–244CrossRefPubMedGoogle Scholar
  3. 3.
    Demicheli V et al (2003) Hepatitis B vaccination and multiple sclerosis: evidence from a systematic review. J Viral Hepat 10(5):343–344CrossRefPubMedGoogle Scholar
  4. 4.
    DeStefano F, Verstraeten T, Chen RT (2002) Hepatitis B vaccine and risk of multiple sclerosis. Expert Rev Vaccines 1(4):461–466CrossRefPubMedGoogle Scholar
  5. 5.
    Farez MF, Correale J (2011) Immunizations and risk of multiple sclerosis: systematic review and meta-analysis. J Neurol 258(7):1197–1206CrossRefPubMedGoogle Scholar
  6. 6.
    Gout O (2001) Vaccinations and multiple sclerosis. Neurol Sci 22(2):151–154CrossRefPubMedGoogle Scholar
  7. 7.
    Jefferson T, Heijbel H (2001) Demyelinating disease and hepatitis B vaccination: is there a link? Drug Saf 24(4):249–254CrossRefPubMedGoogle Scholar
  8. 8.
    Loebermann M et al (2011) Vaccination against infection in patients with multiple sclerosis. Nat Rev Neurol 8(3):143–151CrossRefGoogle Scholar
  9. 9.
    Merelli E, Casoni F (2000) Prognostic factors in multiple sclerosis: role of intercurrent infections and vaccinations against influenza and hepatitis B. Neurol Sci 21(4 Suppl 2):S853–S856CrossRefPubMedGoogle Scholar
  10. 10.
    Sievers EJ, Heyneman CA (2002) Relationship between vaccinations and multiple sclerosis. Ann Pharmacother 36(1):160–162CrossRefPubMedGoogle Scholar
  11. 11.
    Ascherio A et al (2001) Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 344(5):327–332CrossRefPubMedGoogle Scholar
  12. 12.
    DeStefano F et al (2003) Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 60(4):504–509CrossRefPubMedGoogle Scholar
  13. 13.
    Eftekharian MM et al (2014) Multiple sclerosis and immunological-related risk factors: results from a case-control study. Hum Antibodies 23(1–2):31–36PubMedGoogle Scholar
  14. 14.
    Geier DA, Geier MR (2005) A case-control study of serious autoimmune adverse events following hepatitis B immunization. Autoimmunity 38(4):295–301CrossRefPubMedGoogle Scholar
  15. 15.
    Hernan MA et al (2004) Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 63(5):838–842CrossRefPubMedGoogle Scholar
  16. 16.
    Hocine MN et al (2007) Hepatitis B vaccination and first central nervous system demyelinating events: reanalysis of a case-control study using the self-controlled case series method. Vaccine 25(31):5938–5943CrossRefPubMedGoogle Scholar
  17. 17.
    Langer-Gould A et al (2014) Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol 71(12):1506–1513CrossRefPubMedGoogle Scholar
  18. 18.
    Mikaeloff Y et al (2007) Hepatitis B vaccine and risk of relapse after a first childhood episode of CNS inflammatory demyelination. Brain 130(Pt 4):1105–1110PubMedGoogle Scholar
  19. 19.
    Mikaeloff Y et al (2007) Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis. Arch Pediatr Adolesc Med 161(12):1176–1182CrossRefPubMedGoogle Scholar
  20. 20.
    Mikaeloff Y et al (2009) Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood. Neurology 72(10):873–880CrossRefPubMedGoogle Scholar
  21. 21.
    Ozakbas S et al (2006) Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes. Tissue Antigens 68(3):235–238CrossRefPubMedGoogle Scholar
  22. 22.
    Ramagopalan SV et al (2009) Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology 32(4):257–262CrossRefPubMedGoogle Scholar
  23. 23.
    Sadovnick AD, Scheifele DW (2000) School-based hepatitis B vaccination programme and adolescent multiple sclerosis. Lancet 355(9203):549–550CrossRefPubMedGoogle Scholar
  24. 24.
    Touze E et al (2002) Hepatitis B vaccination and first central nervous system demyelinating event: a case-control study. Neuroepidemiology 21(4):180–186CrossRefPubMedGoogle Scholar
  25. 25.
    Zipp F, Weil JG, Einhaupl KM (1999) No increase in demyelinating diseases after hepatitis B vaccination. Nat Med 5(9):964–965CrossRefPubMedGoogle Scholar
  26. 26.
    Confavreux C et al (2001) Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med 344(5):319–326CrossRefPubMedGoogle Scholar
  27. 27.
    Chao C et al (2012) Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 271(2):193–203CrossRefPubMedGoogle Scholar
  28. 28.
    Grimaldi-Bensouda L et al (2014) Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J Intern Med 275(4):398–408CrossRefPubMedGoogle Scholar
  29. 29.
    Pellegrino P et al (2013) No evidence of a link between multiple sclerosis and the vaccine against the human papillomavirus. Eur J Epidemiol 28(8):705–707CrossRefPubMedGoogle Scholar
  30. 30.
    Scheller NM et al (2015) Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA 313(1):54–61CrossRefPubMedGoogle Scholar
  31. 31.
    Alter M, Speer J (1968) Clinical evaluation of possible etiologic factors in multiple sclerosis. Neurology 18(2):109–116CrossRefPubMedGoogle Scholar
  32. 32.
    Bardage C et al (2011) Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. Bmj 343:d5956CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zorzon M et al (2003) Risk factors of multiple sclerosis: a case-control study. Neurol Sci 24(4):242–247CrossRefPubMedGoogle Scholar
  34. 34.
    Auriel E et al (2012) Seasonal and H1N1v influenza vaccines in MS: safety and compliance. J Neurol Sci 314(1–2):102–103CrossRefPubMedGoogle Scholar
  35. 35.
    Bamford CR, Sibley WA, Laguna JF (1978) Swine influenza vaccination in patients with multiple sclerosis. Arch Neurol 35(4):242–243CrossRefPubMedGoogle Scholar
  36. 36.
    De Keyser J, Zwanikken C, Boon M (1998) Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis. J Neurol Sci 159(1):51–53CrossRefPubMedGoogle Scholar
  37. 37.
    Farez MF et al (2012) H1N1 vaccination does not increase risk of relapse in multiple sclerosis: a self-controlled case-series study. Mult Scler 18(2):254–256CrossRefPubMedGoogle Scholar
  38. 38.
    McNicholas N, Chataway J (2011) Relapse risk in patients with multiple sclerosis after H1N1 vaccination, with or without seasonal influenza vaccination. J Neurol 258(8):1545–1547CrossRefPubMedGoogle Scholar
  39. 39.
    Michielsens B et al (1990) Serial magnetic resonance imaging studies with paramagnetic contrast medium: assessment of disease activity in patients with multiple sclerosis before and after influenza vaccination. Eur Neurol 30(5):258–259CrossRefPubMedGoogle Scholar
  40. 40.
    Miller AE et al (1997) A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology 48(2):312–314CrossRefPubMedGoogle Scholar
  41. 41.
    Mokhtarian F et al (1997) Influenza virus vaccination of patients with multiple sclerosis. Mult Scler 3(4):243–247CrossRefPubMedGoogle Scholar
  42. 42.
    Moriabadi NF et al (2001) Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurology 56(7):938–943CrossRefPubMedGoogle Scholar
  43. 43.
    Myers LW et al (1977) Swine influenza virus vaccination in patients with multiple sclerosis. J Infect Dis 136(Suppl):S546–S554CrossRefPubMedGoogle Scholar
  44. 44.
    Salvetti M et al (1995) Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination. J Neurol 242(3):143–146CrossRefPubMedGoogle Scholar
  45. 45.
    Sibley WA, Bamford CR, Laguna JF (1976) Influenza vaccination in patients with multiple sclerosis. JAMA 236(17):1965–1966CrossRefPubMedGoogle Scholar
  46. 46.
    Sibley WA, Foley JM (1965) Infection and immunization in multiple sclerosis. Ann N Y Acad Sci 122:457–466CrossRefPubMedGoogle Scholar
  47. 47.
    Ahlgren C et al (2009) A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk. Eur J Epidemiol 24(9):541–552CrossRefPubMedGoogle Scholar
  48. 48.
    Bansil S et al (1997) Multiple sclerosis in India: a case-control study of environmental exposures. Acta Neurol Scand 95(2):90–95CrossRefPubMedGoogle Scholar
  49. 49.
    Kurtzke JF et al (1997) Multiple sclerosis in the Faroe Islands. 7. Results of a case control questionnaire with multiple controls. Acta Neurol Scand 96(3):149–157CrossRefPubMedGoogle Scholar
  50. 50.
    Pekmezovic T, Jarebinski M, Drulovic J (2004) Childhood infections as risk factors for multiple sclerosis: Belgrade case-control study. Neuroepidemiology 23(6):285–288CrossRefPubMedGoogle Scholar
  51. 51.
    Zilber N, Kahana E (1996) Risk factors for multiple sclerosis: a case-control study in Israel. Acta Neurol Scand 94(6):395–403CrossRefPubMedGoogle Scholar
  52. 52.
    Ahlgren C et al (2009) Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations. Acta Neurol Scand 119(5):313–320CrossRefPubMedGoogle Scholar
  53. 53.
    Andersen E, Isager H, Hyllested K (1981) Risk factors in multiple sclerosis: tuberculin reactivity, age at measles infection, tonsillectomy and appendectomy. Acta Neurol Scand 63(2):131–135CrossRefPubMedGoogle Scholar
  54. 54.
    Casetta I et al (1994) Environmental risk factors and multiple sclerosis: a community-based, case-control study in the province of Ferrara, Italy. Neuroepidemiology 13(3):120–128CrossRefPubMedGoogle Scholar
  55. 55.
    Compston DA et al (1986) Viral infection in patients with multiple sclerosis and HLA-DR matched controls. Brain 109(Pt 2):325–344CrossRefPubMedGoogle Scholar
  56. 56.
    Berr C et al (1989) Risk factors in multiple sclerosis: a population-based case-control study in Hautes-Pyrenees, France. Acta Neurol Scand 80(1):46–50CrossRefPubMedGoogle Scholar
  57. 57.
    Ristori G et al (1999) Use of Bacille Calmette–Guerin (BCG) in multiple sclerosis. Neurology 53(7):1588–1589CrossRefPubMedGoogle Scholar
  58. 58.
    Farez MF, Correale J (2011) Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol 68(10):1267–1271CrossRefPubMedGoogle Scholar
  59. 59.
    Baumhackl U et al (2003) A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis. Vaccine 21(Suppl 1):S56–S61CrossRefPubMedGoogle Scholar
  60. 60.
    Quast U, Herder C, Zwisler O (1991) Vaccination of patients with encephalomyelitis disseminata. Vaccine 9(4):228–230CrossRefPubMedGoogle Scholar
  61. 61.
    Ristori G et al (2014) Effects of Bacille Calmette-Guerin after the first demyelinating event in the CNS. Neurology 82(1):41–48CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Pool V, Gordon DM, Decker M (2012) Methodological issues with the risk of relapse study in patients with multiple sclerosis after yellow fever vaccination. Arch Neurol 69(1):144 (author reply 144-5) CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Mia Topsøe Mailand
    • 1
  • Jette Lautrup Frederiksen
    • 2
    Email author
  1. 1.University of CopenhagenCopenhagenDenmark
  2. 2.Department of NeurologyUniversity of Copenhagen, Rigshospitalet GlostrupGlostrupDenmark

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