MS patients on anti-CD20 therapy have robust T cell responses to SARS-CoV-2 vaccination

Scientists from the Johns Hopkins University School of Medicine, USA, have investigated the pattern of immune responses induced by coronavirus disease 2019 (COVID-19) vaccines in multiple sclerosis (MS) patients receiving anti-CD20 therapy. As detailed in the study that is currently available on the medRxiv* preprint server, they have observed that these patients exhibit a robust T cell response despite a reduced humoral response to vaccines.

Study: Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy. Image Credit: Kateryna Kon/ Shutterstock


Therapeutic interventions against MS are known to cause immune suppression, and thus, indirectly increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19. According to available literature, MS patients receiving certain disease-modifying treatments, including anti-CD20 therapies and sphingosine-1-phosphate (S1P)-receptor modulators, may have reduced antibody responses to various existing including COVID-19 vaccines. In contrast, evidence suggests that T cell responses to most of the common vaccines can be maintained in patients receiving anti-CD20 therapies.

In the current study, the scientists have investigated both humoral and T cell immune responses to COVID-19 vaccines in MS patients receiving anti-CD20 therapies or other disease-modifying treatments.

Study design

One hundred and one multiple sclerosis patients who received Pfizer, Moderna, or Johnson & Johnson vaccines were enrolled for the study. Of them, 39 were on anti-CD20 therapy, three were on S1P receptor modulating therapy, and 60 were on other types of disease-modifying therapies (injectables, natalizumab, and non-S1P modulating oral therapies) or no therapy.

Blood samples were collected from the participants four to eight weeks after the final vaccine dose and analyzed for IgG-specific anti-spike S1 antibodies. Similarly, peripheral blood mononuclear cells isolated from blood were analyzed for spike-specific interferon gamma (IFN-γ)-secreting T cell responses.

Humoral immune response

About 56% and 33% of participants on anti-CD20 therapy and S1P receptor modulating therapy, respectively, exhibited antibody responses to COVID-19 vaccines. In contrast, about 94% of participants on other disease-modifying therapies or no therapy exhibited vaccine-induced antibody responses.

Specifically, vaccine-induced antibody responses were observed in 100% of participants who were on injectables or natalizumab, and in 86% of participants who were on other types of disease-modifying therapies. Similarly, all participants who were not receiving any therapy showed robust antibody responses to COVID-19 vaccines.

Cell-mediated immune response

Overall, a robust T cell immune response to COVID-19 vaccines was observed in most participants (86%) receiving either of the mentioned therapies. Interestingly, about 97% of participants on anti-CD20 therapy exhibited spike-specific T cell response, with significantly higher numbers of IFN-γ-secreting cells than that observed in participants receiving other disease-modifying therapies or no therapy.

Study significance

The study reveals an important finding that MS patients receiving immunosuppressive treatments, including anti-CD20 therapy, exhibit a strong T cell response to COVID-19 vaccines, despite a reduced antibody response.

Compared to other disease-modifying therapies, anti-CD20 therapy is associated with a more robust T cell response in MS patients. In contrast, non-anti-CD20 therapies are associated with both humoral and cellular immune responses to COVID-19 vaccines.

Since B cells are required to produce antibodies and activate CD4+ and CD8+ T cells, B cell-depleting therapies like anti-CD20 therapies are expected to suppress both humoral and T cell responses. However, a robust T cell response observed in patients with anti-CD20 treatment could be due to the depletion of regulatory B cells involved in the inhibition of T cell activation. Another reason could be the alleviation of B cell-mediated regulatory T cell activation.

Other studies show that a robust T cell response induced by natural infection is associated with lower COVID-19 severity. Given this observation, the scientists suggest that MS patients receiving anti-CD20 therapy could still achieve some level of protection from vaccination even in the absence of sufficient antibody response.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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