Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era

Abstract

People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses. This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4⁺ T cells are essential to facilitate CD8⁺ T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs-such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells-have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available, decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.

Keywords: COVID-19; Multiple sclerosis; SARS-CoV-2; Vaccines.

Fig. 1

Immune response to vaccination. a Occurs in multiple steps: (1) An APC (e.g., dendritic cells, macrophage, or B cell) recognizes vaccine antigen, resulting in local inflammation; and internalizes, processes, and presents antigen to CD4⁺ T cell in MHC class II. (2) Antigen-specific T cell becomes activated, differentiates, and secretes cytokines to support B cell activation. B cells become activated via interaction with T cells (contact-dependent or contact-independent [involving cytokines]) and differentiate into plasma cell/plasma blast, which produces neutralizing antibodies that can prevent future infection. T (CD4⁺ and CD8⁺) and B cells proliferate, but dendritic cells become limited to support continued differentiation. B cells take over to help continued differentiation and proliferation of T cells by providing late co-stimulatory signals and secretion of cytokines/survival signals that enhance T cell memory formation. (3) Optimal immune memory results (i.e., more memory CD8⁺ T cells, better survival, and enhanced cytotoxicity). Approximately 10% of activated B and T cells become memory cells to help prevent disease in the future. Without B cells, suboptimal memory results (fewer cells, poor survival, and decreased cytotoxicity in cells that remain). b B and T cell interactions are bidirectional and form an integral part of the immune response to vaccination. APC antigen-presenting cell, MHC major histocompatibility complex