Live-attenuated vaccines provide robust immunity against diseases like tuberculosis, measles, mumps, rubella, polio, yellow fever, dengue, typhoid fever, and varicella, with just one or a few doses. However, concerns arise regarding potential pathogen reversion to virulence, which is particularly risky for immunocompromised individuals, contraindicating their administration in multiple sclerosis (MS) patients under modified disease treatments due to the possibility of triggering infections, or stimulating the immune system, precipitating new exacerbations. On the contrary, these vaccines offer enduring immunity that is crucial for protecting MS patients from endemic infectious diseases, leading to severe complications if contracted. These concerns underscore the complex balance between vaccination benefits and the risks of exacerbating MS in patients residing in regions with endemic diseases. This review explores the challenges and considerations associated with their use in MS patients, aiming to maximize benefits while minimizing risks.
Committee to Review Adverse Effects of Vaccines, Institute of Medicine; StrattonKFordA, et al. Adverse effects of vaccines: Evidence and causality. Washington, DC: National Academies Press, 2011.
2.
ThompsonAJBaranziniSEGeurtsJ, et al. Multiple sclerosis. Lancet2018; 391(10130): 1622–1636.
3.
WilliamsonEMBergerJR. Infection risk in patients on multiple sclerosis therapeutics. CNS Drugs2015; 29(3): 229–244.
4.
CorrealeJFiolMGilmoreW. The risk of relapses in multiple sclerosis during systemic infections. Neurology2006; 67(4): 652–659.
5.
BuljevacDFlachHZHopWC, et al. Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain2002; 125(Pt. 5): 952–960.
6.
FarezMFCorrealeJArmstrongMJ, et al. Practice guideline update summary: Vaccine-preventable infections and immunization in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology2019; 93(13): 584–594.
7.
Otero-RomeroSLebrun-FrénayCReyesS, et al. ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs. Mult Scler2023; 29(8): 904–925.
8.
MinorPD. Live attenuated vaccines: Historical successes and current challenges. Virology2015; 479–480: 379–392.
9.
KameiK. Live attenuated vaccines in patients receiving immunosuppressive agents. Pediatr Nephrol2023; 38(12): 3889–3900.
YehMTBujakiEDolanPT, et al. Engineering the live-attenuated polio vaccine to prevent reversion to virulence. Cell Host Microbe2020; 27(5): 736–751.
17.
EtemadifarMNouriHPitzalisM, et al. Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis. J Neurol Neurosurg Psychiatry2022; 93(9): 986–994.
18.
Multiple Sclerosis Therapy Consensus Group (MSTCG); WiendlHToykaKV, et al. Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. J Neurol2008; 255(10): 1449–1463.
19.
RivaABarcellaVBenattiSV, et al. Vaccinations in patients with multiple sclerosis: A Delphi consensus statement. Mult Scler2021; 27(3): 347–359.
20.
ApostolidisSAKakaraMPainterMM, et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat Med2021; 27(11): 1990–2001.
21.
ZhuangZZhuoJYuanY, et al. Harnessing T-cells for enhanced vaccine development against viral infections. Vaccines2024; 12(5): 478.
22.
LunaGAlpingPBurmanJ, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol2020; 77(2): 184–191.
23.
WinkelmannALoebermannMBarnettM, et al. Vaccination and immunotherapies in neuroimmunological diseases. Nat Rev Neurol2022; 18(5): 289–306.
24.
PaybastSSahraianMANahayatiMA, et al. Investigation of the safety of live attenuated varicella-zoster virus vaccination in patients with relapse-remitting multiple sclerosis treated with natalizumab: A case series and review of the literature. Mult Scler Relat Disord2023; 77: 104793.
25.
LebrunCVukusicS and French Group for Recommendations in Multiple Sclerosis (France4MS) and the Société Francophone de la Sclérose En Plaques (SFSEP). Immunization and multiple sclerosis: Recommendations from the French multiple sclerosis society. Mult Scler Relat Disord2019; 31: 173–188.
26.
CarvajalRTurCMartínez-GómezX, et al. A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients. Mult Scler2023; 29(14): 1841–1848.
KrajncNBstehGBergerT, et al. Monoclonal antibodies in the treatment of relapsing multiple sclerosis: An overview with emphasis on pregnancy, vaccination, and risk management. Neurotherapeutics2022; 19(3): 753–773.
30.
Bar-OrAO’BrienSMSweeneyML, et al. Clinical perspectives on the molecular and pharmacological attributes of anti-CD20 therapies for multiple sclerosis. CNS Drugs2021; 35(9): 985–997.
WallisJShentonDPCarlisleRC. Novel approaches for the design, delivery and administration of vaccine technologies. Clin Exp Immunol2019; 196(2): 189–204.
33.
PolandGAOvsyannikovaIGKennedyRB. Personalized vaccinology: A review. Vaccine2018; 36(36): 5350–5357.
34.
ShimabukuroTTNguyenMMartinD, et al. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine2015; 33(36): 4398–4405.
HuoCWuHXiaoJ, et al. Genomic and bioinformatic characterization of mouse mast cells (P815) upon different influenza a virus (H1N1, H5N1, and H7N2) infections. Front Genet2019; 10: 595.
37.
IvanovaVShahabuddinASMSharkeyA, et al. Advancing immunization coverage and equity: A structured synthesis of pro-equity strategies in 61 Gavi-supported countries. Vaccines2023; 11(1): 191.
38.
Medical Advisory Committee of the Immune Deficiency Foundation; ShearerWTFleisherTA, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol2014; 133(4): 961–966.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
