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

Front Immunol. 2024 Aug 19:15:1431403. doi: 10.3389/fimmu.2024.1431403. eCollection 2024.

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 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.

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 (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.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adult
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Argentina
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunity, Humoral
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis* / drug therapy
  • Multiple Sclerosis* / immunology
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Immunosuppressive Agents
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from Novartis Argentina and donations from Merck Argentina and Synthon Bagó. The funds were used exclusively devoted for the purchase of materials and reagents. The principal investigator, BS, obtained a research grant from the Ministry of Health of the City of Buenos Aires (GCBA) to carry out this work.