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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1431403

DOI=10.3389/fimmu.2024.1431403

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>There 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.</p></sec><sec><title>Methods</title><p>IgG 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 2<sup>nd</sup> dose (Sputnik V or AZD1222) and 3<sup>nd</sup> dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed.</p></sec><sec><title>Results</title><p>Multivariate 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 (r<sup>2</sup> adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p&lt;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.</p></sec><sec><title>Discussion</title><p>Findings regarding humoral and cellular response are consistent with previous reports.</p></sec>