Do immunosuppressive treatments influence immune responses against adenovirus-based COVID-19 vaccines in patients with multiple sclerosis? An Argentine multicenter study

Author:

Silva Berenice Anabel,Miglietta Esteban,Casabona Juan Cruz,Wenker Shirley,Eizaguirre María Bárbara,Alonso Ricardo,Casas Magdalena,Lázaro Luciana Grimanesa,Man Federico,Portuondo Gustavo,Lopez Bisso Abril,Zavala Noelia,Casales Federico,Imhoff Gastón,Steinberg Dra Judith,López Pablo Adrián,Carnero Contentti Edgar,Deri Norma,Sinay Vladimiro,Hryb Javier,Chiganer Edson,Leguizamon Felisa,Tkachuk Verónica,Bauer Johana,Ferrandina Flavia,Giachello Susana,Henestroza Paula,Garcea Orlando,Pascuale Carla Antonela,Heitrich Mauro,Podhajcer Osvaldo L.,Vinzón Sabrina,D’Alotto-Moreno Tomas,Benatar Alejandro,Rabinovich Gabriel Adrián,Pitossi Fernando J.,Ferrari Carina C.

Abstract

IntroductionThere are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2.MethodsIgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.ResultsMultivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population.DiscussionFindings regarding humoral and cellular response are consistent with previous reports.

Publisher

Frontiers Media SA

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