Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies

Abstract

Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and COVID-19 vaccination. Here, the humoral and cellular responses are analyzed in a group of aCD20-MS patients (n=43) compared to a healthy control cohort (n=34) during the first 6 months after a 2-dose cycle mRNA-based COVID-19 vaccination. Both IgG antibodies recognizing receptor binding domain (RBD) from CoV-2 spike protein and their blocking activity against RBD-hACE2 binding were significantly reduced in aCD20-MS patients, with a seroconversion rate of only 23.8%. Interestingly, even under conditions of severe B-cell depletion and failed seroconversion, a significantly higher polyfunctional IFNγ+ and IL-2+ T-cell response and strong T-cell proliferation capacity were detected compared to controls. Moreover, no difference in T-cell response was observed between forms of disease (relapsing remitting- vs progressive-MS), anti-CD20 therapy (Rituximab vs Ocrelizumab) and type of mRNA-based vaccine received (mRNA-1273 vs BNT162b2). These results suggest the generation of a partial adaptive immune response to COVID-19 vaccination in B-cell depleted MS individuals driven by a functionally competent T-cell arm. Investigation into the role of the cellular immune response is important to identifying the level of protection against SARS-CoV-2 in aCD20-MS patients and could have potential implications for future vaccine design and application.

Vaccine-based clinical protection against SARS-CoV-2 infection and the humoral immune response: A 1-year follow-up study of patients with multiple sclerosis receiving ocrelizumab

“…Several studies assessing the humoral and cellular immune responses following severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination found reduced anti-SARS-CoV-2(S)-antibody titers and an impaired SARS-CoV-2-specific T cell response in subgroups of pwMS, depending on the DMT regimen. Specifically, pwMS receiving B cell modulating therapies (Bcmts) exhibited a reduced humoral immune response, while T cell-mediated immunity was preserved, which was also demonstrated by our own previous study evaluating a cohort of 59 ocrelizumab-treated pwMS (OCR-pwMS) (1)(2)(3)(4)(5). Longterm data indicate a weakened and short-lasting humoral response to SARS-CoV-2 vaccination in those patients (6).…”

mRNA Vaccines against SARS-CoV-2: Advantages and Caveats

“…This is specially the case for organ-transplanted patients or patients suffering multiple sclerosis. These patients did not benefit from BNT162b2 and mRNA-1273 vaccines due to their immunosuppressive treatments [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. On the other hand, the efficacy of these vaccines has been demonstrated in patients with several types of cancers.…”

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination

“…19,26 PwMS treated with anti-CD20 DMTs have consistently been shown to have low rates of seroconversion but relatively normal T-cell responses to SARS-CoV2 after COVID-19 vaccination. [27][28][29][30][31][32][33][34][35][36][37] In contrast, in people treated with S1P modulators, initial COVID-19 vaccination is associated with attenuated humoral response but that responds somewhat to re-vaccination, while persistently low or absent T-cell responses to SARS-CoV2 are seen in this group. 31,33,35,36,38 It is also likely that changes in the treatment of COVID-19, emerging concurrently with the provision of booster vaccines, may have improved outcomes for pwMS on treatments associated with reduced vaccine responses who developed COVID-19 after vaccine 3.…”

“…19,26 PwMS treated with anti-CD20 DMTs have consistently been shown to have low rates of seroconversion but relatively normal T-cell responses to SARS-CoV2 after COVID-19 vaccination. 27–37 In contrast, in people treated with S1P modulators, initial COVID-19 vaccination is associated with attenuated humoral response but that responds somewhat to re-vaccination, while persistently low or absent T-cell responses to SARS-CoV2 are seen in this group. 31,33,35,36,38…”