Effects of MS disease-modifying therapies on responses to vaccinations: A review

John Robert Ciotti, Manouela V Valtcheva, Anne Haney Cross, John Robert Ciotti, Manouela V Valtcheva, Anne Haney Cross

Abstract

Background: Development of long-term immunologic memory relies upon humoral and cellular immune responses. Vaccinations aim to stimulate these responses against pathogens. Several studies have evaluated the impact of multiple sclerosis disease-modifying therapies on immune response to vaccines. Findings from these studies have important implications for people with multiple sclerosis who require vaccination and are using disease-modifying therapies.

Methods: Searches using PubMed and other engines were conducted in May 2020 to collect studies evaluating the impact of various disease-modifying therapies on immune responses to vaccination.

Results: Several studies demonstrated preserved immune responses in people treated with beta-interferons to multiple vaccine types. Limited data suggest vaccine responses to be preserved with dimethyl fumarate treatment, as well. Vaccine responses were reduced to varying degrees in those treated with glatiramer acetate, teriflunomide, sphingosine-1-phosphate receptor modulators, and natalizumab. The timing of vaccination played an important role in those treated with alemtuzumab. Humoral vaccine responses were significantly impaired by B cell depleting anti-CD20 monoclonal antibody therapies, particularly to a neoantigen. Data are lacking on vaccine responses in patients with multiple sclerosis taking cladribine and high-dose corticosteroids. Notably, the majority of these studies have focused on humoral responses, with few examining cellular immune responses to vaccination.

Conclusions: Prior investigations into the effects of individual disease-modifying therapies on immune responses to existing vaccines can serve as a guide to expected responses to a SARS-CoV-2 vaccine. Responses to any vaccination depend on the vaccine type, the type of response (recall versus response to a novel antigen), and the impact of the individual disease-modifying therapy on humoral and cellular immunity in response to that vaccine type. When considering a given therapy, clinicians should weigh its efficacy against MS for the individual patient versus potential impact on responses to vaccinations that may be needed in the future.

Keywords: Disease-modifying therapies; Multiple sclerosis; Vaccines.

Conflict of interest statement

Declaration of Competing Interest John R. Ciotti has received funding from the Biogen MS Clinical Fellowship Program. Manouela V. Valtcheva has nothing to disclose. Anne H. Cross is funded by the Manny & Rosalyn Rosenthal – Dr. John L. Trotter MS Center Chair in Neuroimmunology. She has also received consulting and/or speaking fees from Biogen, Celgene, EMD Serono, Genentech/Roche, Novartis and Race to Erase MS.

Copyright © 2020 Elsevier B.V. All rights reserved.

References

    1. Wallin M.T., Culpepper W.J., Campbell J.D., et al. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology. 2019;92(10):E1029–E1040. doi: 10.1212/WNL.0000000000007035.
    1. Clem A.S.Fundamentals of vaccine immunology. In: J. Glob. Infect. Dis.. Vol 3.; 2011:73–78. doi:10.4103/0974-777X.77299.
    1. Ayling K., Vedhara K., Fairclough L. Vol. 2018. Humana Press Inc; 1781. Measuring vaccine responses in the multiplex era. pp. 327–340. (Methods in Molecular Biology).
    1. Zacour M., Ward B.J., Brewer A., et al. Standardization of Hemagglutination Inhibition Assay for Influenza Serology Allows for High Reproducibility between Laboratories. Clin. Vaccine Immunol. 2016;23(3):236–242. doi: 10.1128/CVI.00613-15.
    1. Flanagan K.L., Fink A.L., Plebanski M., Klein S.L. Sex and Gender Differences in the Outcomes of Vaccination over the Life Course. Annu. Rev. Cell Dev. Biol. 2017;33(1):577–599. doi: 10.1146/annurev-cellbio-100616-060718.
    1. Mailand M.T., Frederiksen J.L. Vaccines and multiple sclerosis: a systematic review. J. Neurol. 2017;264(6):1035–1050. doi: 10.1007/s00415-016-8263-4.
    1. Stratton K., Ford A., Rusch E., Clayton E.W. National Academies Press; 2012. Adverse Effects of Vaccines: Evidence and Causality.
    1. Moriabadi N.F., Niewiesk S., Kruse N., et al. Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurology. 2001;56(7):938–943. doi: 10.1212/WNL.56.7.938.
    1. Miller A.E., Morgante L.A., Buchwald L.Y., et al. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology. 1997;48(2):312–314. doi: 10.1212/wnl.48.2.312.
    1. Scheller N.M., Svanström 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. doi: 10.1001/jama.2014.16946.
    1. Auriel E., Gadoth A., Regev K., Karni A. Seasonal and H1N1v influenza vaccines in MS: safety and compliance. J. Neurol. Sci. 2012;314(1–2):102–103. doi: 10.1016/j.jns.2011.10.013.
    1. Confavreux C., Suissa S., Saddier P., Bourdes V., Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N. Engl. J. Med. 2001;344(5):319–326.
    1. Langer-Gould A., Qian L., Tartof S.Y., et al. Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol. 2014;71(12):1506–1513. doi: 10.1001/jamaneurol.2014.2633.
    1. ACIP Altered Immunocompetence Guidelines for Immunizations | Recommendations | CDC. .
    1. Lebrun C., Vukusic S. Immunization and multiple sclerosis: recommendations from the French multiple sclerosis society. Mult. Scler. Relat. Disord. 2019;31:173–188. doi: 10.1016/j.msard.2019.04.004.
    1. Epstein D.J., Dunn J., Deresinski S. Infectious Complications of Multiple Sclerosis Therapies: implications for Screening, Prophylaxis, and Management. Open forum Infect. Dis. 2018;5(8) doi: 10.1093/ofid/ofy174. ofy174.
    1. Loebermann M., Winkelmann A., Hartung H.P., Hengel H., Reisinger E.C., Zettl U.K. Vaccination against infection in patients with multiple sclerosis. Nat. Rev. Neurol. 2012;8(3):143–151. doi: 10.1038/nrneurol.2012.8.
    1. OCEBM Levels of Evidence - CEBM. .
    1. Schwid S.R., Decker M.D., Lopez-Bresnahan M. Immune response to influenza vaccine is maintained in patients with multiple sclerosis receiving interferon beta-1a. Neurology. 2005;65(12):1964–1966. doi: 10.1212/01.wnl.0000188901.12700.e0.
    1. Bar-Or A., Freedman M.S., Kremenchutzky M., et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552–558. doi: 10.1212/WNL.0b013e31829e6fbf.
    1. Mehling M., Fritz S., Hafner P., et al. Preserved antigen-specific immune response in patients with multiple sclerosis responding to IFNβ-therapy. PLoS ONE. 2013;8(11) doi: 10.1371/journal.pone.0078532.
    1. Olberg H.K., Cox R.J., Nostbakken J.K., Aarseth J.H., Vedeler C.A., Myhr K.M. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult. Scler. J. 2014;20(8):1074–1080. doi: 10.1177/1352458513513970.
    1. Olberg H.K., Eide G.E., Cox R.J., et al. Antibody response to seasonal influenza vaccination in patients with multiple sclerosis receiving immunomodulatory therapy. Eur J Neurol. 2018;25(3):527–534. doi: 10.1111/ene.13537.
    1. Von Hehn C., Howard J., Liu S., et al. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol. Neuroimmunol. NeuroInflammation. 2018;5(1) doi: 10.1212/NXI.0000000000000409.
    1. Metze C., Winkelmann A., Loebermann M., et al. Immunogenicity and predictors of response to a single dose trivalent seasonal influenza vaccine in multiple sclerosis patients receiving disease-modifying therapies. CNS Neurosci. Ther. 2019;25(2):245–254. doi: 10.1111/cns.13034.
    1. Bar-Or A., Wiendl H., Miller B., et al. Randomized study of teriflunomide effects on immune responses to neoantigen and recall antigens. Neurol. Neuroimmunol. NeuroInflammation. 2015;2(2):e70. doi: 10.1212/NXI.0000000000000070.
    1. Mehling M., Hilbert P., Fritz S., et al. Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients. Ann. Neurol. 2011;69(2):408–413. doi: 10.1002/ana.22352.
    1. Kappos L., Mehling M., Arroyo R., et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872–879. doi: 10.1212/WNL.0000000000001302.
    1. Ufer M., Shakeri-Nejad K., Gardin A., et al. Impact of siponimod on vaccination response in a randomized, placebo-controlled study. Neurol. Neuroimmunol. neuroinflammation. 2017;4(6):e398. doi: 10.1212/NXI.0000000000000398.
    1. Vågberg M., Kumlin U., Svenningsson A. Humoral immune response to influenza vaccine in natalizumab-treated MS patients. Neurol. Res. 2012;34(7):730–733. doi: 10.1179/1743132812Y.0000000059.
    1. Kaufman M., Pardo G., Rossman H., Sweetser M.T., Forrestal F., Duda P. Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis. J. Neurol. Sci. 2014;341(1–2):22–27. doi: 10.1016/j.jns.2014.03.035.
    1. Stokmaier D., Winthrop K., Chognot C., et al. Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis (S36.002) Neurology. 2018;90(15 Supplement)
    1. Bingham C.O., Looney R.J., Deodhar A., et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010;62(1):64–74. doi: 10.1002/art.25034.
    1. McCarthy C.L., Tuohy O., Compston D.A.S., Kumararatne D.S., Coles A.J., Jones J.L. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872–876. doi: 10.1212/WNL.0b013e3182a35215.
    1. Briggs W.A., Rozek R.J., Migdal S.D., et al. Influenza vaccination in kidney transplant recipients: cellular and humoral immune responses. Ann. Intern. Med. 1980;92(4):471–477. doi: 10.7326/0003-4819-92-4-471.
    1. Lahood N., Emerson S.S., Kumar P., Sorensen R.U. Antibody levels and response to pneumococcal vaccine in steroid-dependent asthma. Ann. Allergy. 1993;70(4):289–294.
    1. Elkayam O., Paran D., Caspi D., et al. Immunogenicity and Safety of Pneumococcal Vaccination in Patients with Rheumatoid Arthritis or Systemic Lupus Erythematosus. Clin. Infect Dis. 2002;34(2):147–153. doi: 10.1086/338043.
    1. Wallin L., Quintilio W., Locatelli F., Cassel A., Silva M.B., Skare T.L. Safety and efficiency of influenza vaccination in systemic lupus erythematosus patients. Acta Reumatol. Port.. 34(3):498–502.
    1. Rubin L.G., Levin M.J., Ljungman P., et al. IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin. Infect. Dis. 2013;58(3):309–318. doi: 10.1093/cid/cit816. 2014.
    1. Draft landscape of COVID-19 candidate vaccines. Accessed June26, 2020. .

Source: PubMed

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