Vaccines and Multiple Sclerosis

The capacity of vaccines to either cause or exacerbate multiple sclerosis has been evaluated in several excellent studies.

Two large studies evaluated whether the hepatitis B vaccine causes multiple sclerosis or whether hepatitis B, tetanus or influenza vaccines worsen symptoms of multiple sclerosis. The first study evaluated 121,700 nurses followed from 1976 and 116,671 nurses followed from 1989 to identify 192 women with multiple sclerosis and 645 matched controls. There was no association between receiving the hepatitis B vaccine or the number of doses of hepatitis B vaccine and the risk of multiple sclerosis. The second study included 643 patients with a relapse of symptoms of multiple sclerosis occurring between 1993 and 1997 identified from the European Database for Multiple Sclerosis. The risk of relapse was not associated with the use of any of the vaccines studied (i.e., hepatitis B, tetanus and influenza vaccines).

Additional well-controlled studies also found that influenza vaccine did not exacerbate symptoms of multiple sclerosis. Indeed, in a study of 180 patients with relapsing multiple sclerosis, infection with influenza virus was more likely than immunization with influenza vaccine to cause a worsening of symptoms. Because natural influenza virus is well adapted to growth in people, and because the influenza vaccine shot does not contain replicating virus, natural infection is more likely than vaccination to worsen symptoms of multiple sclerosis. Taken together, these findings suggest that influenza vaccine is more likely to prevent than cause exacerbations of multiple sclerosis.

Other studies, listed below, further confirm that vaccines against hepatitis B, HPV, tetanus, influenza, measles, mumps, rubella, variola, BCG, polio, and diphtheria do not appear to either cause or exacerbate symptoms of multiple sclerosis.

References

Hepatitis B vaccine and MS

Mouchet J, Salvo F, Raschi E, et al. Hepatitis B vaccination and the putative risk of central demyelinating diseases—A systematic review and meta-analysis. Vaccine 2018; 36:1548-1555.
The authors conducted a systematic review of the medical and scientific literature through 2017 finding no relationship between receipt of hepatitis B immunization (HBV) and development of central demyelinating diseases.

Mailand MT and JL Frederiksen. Vaccines and multiple sclerosis: a systematic review. J Neurol 2017; 264:1035-1050. 
The authors reviewed the medical literature finding no change in the risk of developing MS after vaccination against HBV, HPV, influenza, MMR, variola, tetanus, BCG, polio or diphtheria.

Langer-Gould A, Qian L, Tartof SY, et al. Vaccines and risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA 2014;71(12):1506-1513.
The authors investigated whether vaccines against hepatitis B (HBV) and human papillomavirus (HPV) increased the risk of multiple sclerosis or other acquired central nervous system demyelinating syndromes (CNS ADS), including acute disseminated encephalomyelitis (ADEM), idiopathic transverse myelitis (TM), optic neuritis (ON), and monofocal or multifocal clinically isolated syndrome (CIS). They found no associations between HBV, HPV or any vaccination and the risk of MS or CNS ADS up to three years following vaccination. An increased risk of CNS ADS was observed within 30 days after of vaccination in some younger patients; however, this association disappeared after 30 days suggesting that, at most, vaccines revealed but did not cause pre-existing autoimmunity.

Mikaeloff Y, Caridade G, Rossier M, et al. Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis.  Arch Pediatr Adolesc Med 2007;161(12):1176-1182.
The authors found that hepatitis B vaccination (HBV) did not increase the risk of multiple sclerosis (MS) in childhood within the three-year study period.

Ozakbas S, Idiman E, Yulug B, et al. Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes. Tissue Antigens 2006;68: 235-238.
The authors compared the clinical courses of patients who developed MS after HBV with MS patients without a history of HBV. No differences were observed in the clinical features between vaccinated and unvaccinated MS patients. The authors concluded that HBV is safe in MS patients and not involved in the development of MS.

DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60:504-509.
The authors evaluated the relationship between vaccination and multiple sclerosis (MS) or optic neuritis (ON) among adults 18-49 years of age within three large health maintenance organizations. They found that hepatitis B, influenza, tetanus, measles or rubella vaccines were not associated with an increased risk of MS or ON.

Ascherio A, Zhang SM, Hernan MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001; 344:327-332. 
The authors performed a large case-control study of nurses in the United States finding no association between HBV and the development of MS, including no correlation with total number of doses received.

Confavreux C, Suissa S, Saddier P, et al. Vaccinations and the risk of relapse in multiple sclerosis. New Engl J Med 2001; 344(5):319-326.
The authors found that tetanus, HBV, or influenza vaccination did not increase the short-term risk of relapse in patients with MS.

Sadovnick AD and DW Scheifele. School-based hepatitis B vaccination programme and adolescent multiple sclerosis. Lancet 2000;355:549-550.
The authors investigated MS in adolescents in British Columbia before and after a HBV program was initiated. They found no differences in the incidence of MS for students 11-12 years of age.

Human papillomavirus (HPV) vaccine and multiple sclerosis/central demyelinating disease

Mouchet J, Salvo F, Raschi E, et al. Human papillomavirus vaccine and demyelinating diseases—a systematic review and meta-analysis. Pharmacol Res 2018;132:108-118.
The authors conducted a systematic review of all published literature through May 2017 to assess the risk of developing demyelination after HPV immunization. They found no significant association between HPV vaccination and central demyelination, multiple sclerosis, or optic neuritis.

Mailand MT and JL Frederiksen. Vaccines and multiple sclerosis: a systematic review. J Neurol 2017; 264:1035-1050. 
The authors reviewed the medical literature regarding the role of vaccines in the development of multiple sclerosis (MS) or MS relapse. They found no change in the risk of developing MS after vaccination against HBV, HPV, seasonal influenza, MMR, variola, tetanus, BCG, polio or diphtheria. No change in the risk of relapse was found following influenza vaccination.

Grimaldi-Bensouda L, Rossignol M, Kone-Paut I, et al. Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: six years of case-referent surveillance. J Autoimmun 2017; 19:84-90.
The authors assessed the risk of autoimmune diseases associated with HPV vaccination of females 11-25 years of age over a 6 ½--year period. They found no association between HPV vaccination and central demyelination, multiple sclerosis, connective tissue disease, Guillain-Barré syndrome, type 1 diabetes, autoimmune thyroiditis, and idiopathic thrombocytopenic purpura. 

Dhar JP, Essenmacher L, Dhar R, et al. The safety and immunogenicity of quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus. Vaccine 2017;35:2642-2646.
The authors evaluated the safety and immunogenicity of HPV vaccine in systemic lupus erythematosus (SLE) in women aged 19-50 years with mild to moderate SLE and minimally active or inactive SLE. Nine serious adverse events occurred, though none were related to vaccine or SLE. No patients experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies. The authors concluded that HPV vaccine was generally safe, well tolerated, and highly immunogenic.

Gronlund O, Herweijer E, Sundstrom K, et al. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study. J Int Med 2016;280:618-626.
The authors assessed whether HPV vaccination was associated with an increased incidence of new-onset autoimmune disease in more than 70,000 girls and women (10-30 years of age) with pre-existing autoimmune diseases. They found that HPV vaccination was not associated with new-onset autoimmune diseases in this patient population.

Scheller NM, Svanstrom H, Pasternak B, et al. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA 2015;313(1):54-61.
The authors investigated the association of HPV vaccination and risk of multiple sclerosis and other demyelinating diseases among females 10-44 years of age in Denmark and Sweden. Nearly 4,000,000 females were evaluated, including more than 789,000 who received HPV vaccine. The authors found no increased risk of multiple sclerosis or other demyelinating diseases such as optic neuritis, neuromyelitis optica, transverse myelitis, or acute disseminated encephalomyelitis following vaccination.

Langer-Gould A, Qian L, Tartof SY, et al. Vaccines and risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA 2014;71(12):1506-1513.
The authors investigated whether vaccines, particularly HBV and HPV, increased the risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes including acute disseminated encephalomyelitis (ADEM), idiopathic transverse myelitis (TM), optic neuritis (ON), and monofocal or multifocal clinically isolated syndrome (CIS). They found no associations between HBV, HPV or any vaccination and the risk of MS or acute demyelinating syndromes up to three years later.

Flu vaccine and multiple sclerosis/CNS demyelinating diseases

Mailand MT and JL Frederiksen. Vaccines and multiple sclerosis: a systematic review. J Neurol 2017; 264:1035-1050. 
The authors reviewed the medical literature on the role of vaccines in the development of multiple sclerosis (MS) or relapse. They found no change in the risk of developing MS after vaccination against HBV, HPV, seasonal influenza, MMR, variola, tetanus, BCG, polio or diphtheria. Similarly, no change in the risk of relapse was found following immunization against influenza.

DeStefano F, Verstraeten T, Jackson LA, et al.  Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003;60:504-509.
The authors evaluated the association between vaccination and the onset of multiple sclerosis (MS) or optic neuritis (ON) among adults 18 to 49 years of age within three large health maintenance organizations by investigating the onset of first symptoms at any time after vaccination and during specified intervals after vaccination. They found that vaccination against hepatitis B, influenza, tetanus, measles or rubella was not associated with an increased risk of MS or ON.

Confavreux C, Suissa S, Saddier P, et al.  Vaccinations and the risk of relapse in multiple sclerosis. New Engl J Med 2001; 344(5):319-326.
The authors found that tetanus, hepatitis B, and influenza vaccines did not increase the short-term risk of relapse in adult patients with MS.

Moriabadi NF, Niewiesk S, Kruse N, Jung S, Weissbrich B, et al.  Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurol 2001; 56:938-943.
The authors examined influenza A virus-specific and myelin basic protein-specific T-cell frequencies in patients with MS and healthy controls who received influenza vaccine.  Both groups responded to the vaccine as evidenced by an antibody response, but no increase in T-cell frequencies responsive to human myelin basic protein or recombinant human myelin oligodendrocyte protein was observed after immunization. The authors concluded that these data support the clinical observations that influenza vaccination is effective and safe in patients with MS.

Miller AE, Morgante LA, Buchwald LY, Nutile SM, Coyle PK, et al.  A multicenter, randomized, double blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurol 1997;48;312-314.
The authors determined the clinical effect of influenza vaccine in patients with relapsing/remitting MS. No differences were found between vaccine and placebo recipients in the attack rate or disease progression over 6 months. They concluded that influenza immunization in MS patients is neither associated with an increased exacerbation rate in the post-vaccination period nor with a change in disease course over the subsequent six months.

Michielsens B, Wilms G, Marchal G, Carton H. 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 1990;30(5):258-259.
The authors examined patients with a relapsing-remitting form of MS to determine if influenza vaccination affected the clinical course. Patients were examined clinically as well as with MRI scans three weeks before vaccination, the day of vaccination, and three weeks after vaccination. The authors found no exacerbations in the pre- or post-vaccination period. On MRI, a greater number of lesions appeared at the end of the pre-vaccination period as compared with post-vaccination. The authors concluded that influenza vaccine has no clinical or subclinical short-term effect on the activity of MS.

Reviewed by Paul A. Offit, MD, Lori Handy, MD, MSCE on September 11, 2018

Materials in this section are updated as new information and vaccines become available. The Vaccine Education Center staff regularly reviews materials for accuracy.

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