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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1431403
This article is part of the Research Topic COVID-19 and the brain - the dawn of a new era in neuroinflammation and demyelination View all 11 articles

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

Provisionally accepted
Berenice A. Silva Berenice A. Silva 1,2,3*Esteban Miglietta Esteban Miglietta 4Juan C. Casabona Juan C. Casabona 2Shirley Wenker Shirley Wenker 2María B. Eizaguirre María B. Eizaguirre 3Ricardo Alonso Ricardo Alonso 3Magdalena Casas Magdalena Casas 3Luciana Grimanesa Lázaro Luciana Grimanesa Lázaro 3Federico Man Federico Man 3Gustavo Portuondo Gustavo Portuondo 3Abril Lopez Bisso Abril Lopez Bisso 3Noelia Zavala Noelia Zavala 3Federico Casales Federico Casales 3Gastón Imhoff Gastón Imhoff 5Dra Judith Steinberg Dra Judith Steinberg 6Pablo Adrián López Pablo Adrián López 7Edgar Carnero Contentti Edgar Carnero Contentti 7Norma Deri Norma Deri 8Vladimiro Sinay Vladimiro Sinay 9Javier Hryb Javier Hryb 10Edson Chiganer Edson Chiganer 10Felisa Leguizamon Felisa Leguizamon 11Verónica Tkachuk Verónica Tkachuk 12Johana Bauer Johana Bauer 13Flavia Ferrandina Flavia Ferrandina 13Susana Giachello Susana Giachello 14Paula Henestroza Paula Henestroza 14Orlando Garcea Orlando Garcea 3Carla A. Pascuale Carla A. Pascuale 4Mauro Heitrich Mauro Heitrich 15Osvaldo L. Podhajcer Osvaldo L. Podhajcer 15Sabrina Vinzón Sabrina Vinzón 15Tomas D'Alotto-Moreno Tomas D'Alotto-Moreno 16Alejandro Benatar Alejandro Benatar 16Gabriel A. Rabinovich Gabriel A. Rabinovich 16FERNANDO J. PITOSSI FERNANDO J. PITOSSI 2Carina C. Ferrari Carina C. Ferrari 2
  • 1 Italian Hospital of Buenos Aires, Buenos Aires, Argentina
  • 2 Laboratorio de Terapias Regenerativas y Protectoras del Sistema Nervioso, Fundación Instituto Leloir IIBBA CONICET, Ciudad autonoma Buenos aires, Argentina
  • 3 Centro Universitario de Esclerosis Múltiple, Hospital Ramos Mejía, Ciudad autonoma Buenos aires, Argentina
  • 4 IIBBA-CONICET Leloir Institute Foundation, Buenos Aires, Buenos Aires, Argentina
  • 5 Sanatorio de los Arcos, Buenos Aires, Argentina
  • 6 Hospital Británico de Buenos Aires, Buenos Aires, Buenos Aires, Argentina
  • 7 Hospital Alemán, Buenos Aires, Buenos Aires, Argentina
  • 8 DIABAID, Buenos Aires, Argentina
  • 9 Fundacion Favaloro Hospital Universitario, Buenos Aires, Buenos Aires, Argentina
  • 10 El Hospital General de Agudos Carlos G. Durand, Buenos Aires, Buenos Aires, Argentina
  • 11 Hospital General de Agudos Dr. TEODORO ALVAREZ, Buenos Aires, Buenos Aires, Argentina
  • 12 Hospital de Clínicas José de San Martín, Buenos Aires, Buenos Aires, Argentina
  • 13 Esclerosis múltiple Argentina, Buenos Aires, Argentina
  • 14 Asociación Lucha Contra la Esclerosis Múltiple, Buenos Aires, Argentina
  • 15 Laboratorio de Terapias Moleculares y Celulares, IIBBA-CONICET Fundación Instituto Leloir, Buenos Aires, Buenos Aires, Argentina
  • 16 Laboratorio de Glicomedicina - IBYME, Buenos Aires, Argentina

The final, formatted version of the article will be published soon.

    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. 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 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. 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 (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. Findings regarding humoral and cellular response are consistent with previous reports.

    Keywords: Multiple Sclerosis, Vaccine, Immune reponse, COVID - 19, Cell response, Omicron (BA.1)

    Received: 11 May 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 Silva, Miglietta, Casabona, Wenker, Eizaguirre, Alonso, Casas, Grimanesa Lázaro, Man, Portuondo, Lopez Bisso, Zavala, Casales, Imhoff, Steinberg, López, Carnero Contentti, Deri, Sinay, Hryb, Chiganer, Leguizamon, Tkachuk, Bauer, Ferrandina, Giachello, Henestroza, Garcea, Pascuale, Heitrich, Podhajcer, Vinzón, D'Alotto-Moreno, Benatar, Rabinovich, PITOSSI and Ferrari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Berenice A. Silva, Italian Hospital of Buenos Aires, Buenos Aires, Argentina

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