Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern

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Azevedo, Patrick O. ; Hojo-Souza, Natalia S. ; Faustino, Lidia P. ; Fumagalli, Marcilio J. ; Hirako, Isabella C. ; Oliveira, Emiliano R. ; Figueiredo, Maria M. ; Carvalho, Alex F. ; Doro, Daniel ; Benevides, Luciana ; Durigon, Edison ; Fonseca, Flavio ; Machado, Alexandre M. ; Fernandes, Ana P. ; Teixeira, Santuza R. ; Silva, Joao S. ; Gazzinelli, Ricardo T.

• Document type: Journal article
• Source: NPJ VACCINES; v. 8, n. 1, p. 17-pg., 2023-02-13.

Abstract

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs. (AU)

• FAPESP's process: 20/05527-0 - Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury
• Grantee: Ricardo Tostes Gazzinelli
• Support Opportunities: Regular Research Grants