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.
Keywords: B-cell; COVID-19; T-cell response; adaptive immunity; anti-CD20; antibodies; multiple sclerosis; vaccination.
【저자키워드】 COVID-19, antibodies, Adaptive immunity, multiple sclerosis, T-cell Response, vaccination., anti-CD20, B-cell, 【초록키워드】 SARS-CoV-2, Adaptive immunity, coronavirus, vaccination, adaptive, multiple sclerosis, Cellular immune response, mRNA-1273, Immunotherapy, T-cell Response, Vaccine design, Infection, severe acute respiratory syndrome Coronavirus, rituximab, anti-CD20 therapy, Spike protein, hACE2, Receptor binding domain, BNT162b2, Cohort, Seroconversion, IgG antibody, COVID-19 vaccination, IgG antibodies, RBD, mRNA, Patient, Complication, virus infection, T-cell, Adaptive immune response, respiratory, disease, patients, anti-CD20, Ocrelizumab, binding, IL-2, B-cell, cellular response, investigation, humoral, antibody production, Humoral and cellular responses, regimen, proliferation, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, immunocompromised individuals, healthy control, individual, no difference, IFNγ, seroconversion rate, blocking activity, mRNA-based vaccine, forms, implication, susceptible, controls, analyzed, significantly, form, receiving, reduced, condition, significantly higher, recognizing, individuals, driven by, competent, mRNA-based, relapsing, strong T-cell, 【제목키워드】 therapy, Patient, T-cell activation, receiving, depleting, Strong,