Long-lasting neutralizing antibodies and T cell response after the third dose of mRNA anti-SARS-CoV-2 vaccine in multiple sclerosis

Abstract

Background and objectivesLong lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. Our study aimed at evaluating the persistence of the elicited amount of neutralizing antibodies (Ab), their activity and T cell response after three doses of anti-SARS-CoV-2 vaccine in pwMS.MethodsWe performed a prospective observational study in pwMS undergoing SARS-CoV-2 mRNA vaccinations. Anti-Region Binding Domain (anti-RBD) of the spike (S) protein immunoglobulin G (IgG) titers were measured by ELISA. The neutralization efficacy of collected sera was measured by SARS-CoV-2 pseudovirion-based neutralization assay. The frequency of Spike-specific IFNγ-producing CD4+ and CD8+ T cells was measured by stimulating Peripheral Blood Mononuclear Cells (PBMCs) with a pool of peptides covering the complete protein coding sequence of the SARS-CoV-2 S.ResultsBlood samples from 70 pwMS (11 untreated pwMS, 11 under dimethyl fumarate, 9 under interferon-γ, 6 under alemtuzumab, 8 under cladribine, 12 under fingolimod and 13 under ocrelizumab) and 24 healthy donors were collected before and up to six months after three vaccine doses. Overall, anti-SARS-CoV-2 mRNA vaccine elicited comparable levels of anti-RBD IgGs, neutralizing activity and anti-S T cell response both in untreated, treated pwMS and HD that last six months after vaccination. An exception was represented by ocrelizumab-treated pwMS that showed reduced levels of IgGs (p<0.0001) and a neutralizing activity under the limit of detection (p<0.001) compared to untreated pwMS. Considering the occurrence of a SARS-CoV-2 infection after vaccination, the Ab neutralizing efficacy (p=0.04), as well as CD4+ (p=0.016) and CD8+ (p=0.04) S-specific T cells, increased in treated COVID+ pwMS compared to uninfected treated pwMS at 6 months after vaccination.DiscussionOur follow-up provides a detailed evaluation of Ab, especially in terms of neutralizing activity, and T cell responses after anti-SARS-CoV-2 vaccination in MS context, over time, considering a wide number of therapies, and eventually breakthrough infection. Altogether, our observations highlight the vaccine response data to current protocols in pwMS and underline the necessity to carefully follow-up anti-CD20- treated patients for higher risk of breakthrough infections. Our study may provide useful information to refine future vaccination strategies in pwMS.

Longitudinal study of immunity toSARS‐CoV2in ocrelizumab‐treatedMSpatients up to 2 years afterCOVID‐19 vaccination

“…46 Robust longitudinal cellular immunity in B‐cell‐depleted MS patients is a consistent finding across multiple studies. 28 , 36 , 47 , 48 , 49 , 50 Booster further raised cytokine responses four to fivefold. This was a similar‐fold increase as after the primary vaccine.…”

“…Studies that fail to detect a rise in anti‐Spike antibody levels following Omicron infection should be interpreted cautiously in this context of assays used. 47 An increase in cellular response after infection in patients who have had two vaccine doses would be expected, given that ancestral T cells efficiently cross‐recognize the Omicron variant of SARS‐CoV‐2. 54 It is less clear why cellular immunity appears to have declined after infections in patients with three vaccine doses.…”

Longitudinal study of immunity to SARS-CoV2 in Ocrelizumab-treated multiple sclerosis patients up to 2 years after COVID-19 vaccination

“…Studies that fail to detect a rise in anti-Spike antibody levels following Omicron infection should be interpreted cautiously in this context of assays used. 44 An increase in cellular response after infection in patients who have had two vaccine doses would be expected, given that ancestral T-cells efficiently cross-recognize the Omicron variant of SARS-CoV-2. 50 It is less clear why cellular immunity appears to have declined after infections in patients with three vaccine doses.…”

“…43 Robust longitudinal cellular immunity in B-cell-depleted MS patients is a consistent finding across multiple studies. 26,33,[44][45][46][47] Booster further raised cytokine responses 4-5-fold. This was a similar-fold increase as after the primary vaccine.…”