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Front Immunol . Do immunosuppressive treatments influence immune responses against adenovirus-based COVID-19 vaccines in patients with multiple scl

tetano

Editor, Senior Moderator
Front Immunol


. 2024 Aug 19:15:1431403.
doi: 10.3389/fimmu.2024.1431403. eCollection 2024. Do immunosuppressive treatments influence immune responses against adenovirus-based COVID-19 vaccines in patients with multiple sclerosis? An Argentine multicenter study

Berenice Anabel Silva[SUP] 1 2 3 [/SUP], Esteban Miglietta[SUP] 4 [/SUP], Juan Cruz Casabona[SUP] 2 [/SUP], Shirley Wenker[SUP] 2 [/SUP], María Bárbara Eizaguirre[SUP] 3 [/SUP], Ricardo Alonso[SUP] 3 [/SUP], Magdalena Casas[SUP] 3 [/SUP], Luciana Grimanesa Lázaro[SUP] 3 [/SUP], Federico Man[SUP] 3 [/SUP], Gustavo Portuondo[SUP] 3 [/SUP], Abril Lopez Bisso[SUP] 3 [/SUP], Noelia Zavala[SUP] 3 [/SUP], Federico Casales[SUP] 3 [/SUP], Gastón Imhoff[SUP] 5 [/SUP], Dra Judith Steinberg[SUP] 6 [/SUP], Pablo Adrián López[SUP] 7 [/SUP], Edgar Carnero Contentti[SUP] 7 [/SUP], Norma Deri[SUP] 8 [/SUP], Vladimiro Sinay[SUP] 9 [/SUP], Javier Hryb[SUP] 10 [/SUP], Edson Chiganer[SUP] 10 [/SUP], Felisa Leguizamon[SUP] 11 [/SUP], Verónica Tkachuk[SUP] 12 [/SUP], Johana Bauer[SUP] 13 [/SUP], Flavia Ferrandina[SUP] 13 [/SUP], Susana Giachello[SUP] 14 [/SUP], Paula Henestroza[SUP] 14 [/SUP], Orlando Garcea[SUP] 3 [/SUP], Carla Antonela Pascuale[SUP] 4 [/SUP], Mauro Heitrich[SUP] 15 [/SUP], Osvaldo L Podhajcer[SUP] 15 [/SUP], Sabrina Vinzón[SUP] 15 [/SUP], Tomas D'Alotto-Moreno[SUP] 16 [/SUP], Alejandro Benatar[SUP] 16 [/SUP], Gabriel Adrián Rabinovich[SUP] 16 [/SUP], Fernando J Pitossi[SUP] 2 [/SUP], Carina C Ferrari[SUP] 2 [/SUP]



Affiliations
Abstract

Introduction: 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.
Methods: 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.
Results: 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<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.
Discussion: Findings regarding humoral and cellular response are consistent with previous reports.

Keywords: COVID - 19; Omicron (BA.1); cell response; immune response; multiple sclerosis; vaccine.

 
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