Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern.
Patrick Orestes de AzevedoNatália Satchiko Hojo-SouzaLídia P FaustinoMarcílio J FumagalliIsabella C HirakoEmiliano R OliveiraMaria M FigueiredoAlex F CarvalhoDaniel DoroLuciana BenevidesEdison DurigonFlávio FonsecaAlexandre M MachadoAna P FernandesSantuza R TeixeiraJoão S SilvaRicardo Tostes GazzinelliPublished in: NPJ vaccines (2023)
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.
Keyphrases
- sars cov
- coronavirus disease
- copy number
- respiratory syndrome coronavirus
- high fat diet induced
- drug induced
- early onset
- type diabetes
- cell free
- regulatory t cells
- dendritic cells
- oxidative stress
- transcription factor
- high glucose
- endothelial cells
- immune response
- genetic diversity
- zika virus
- skeletal muscle
- wild type