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Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 SARS-CoV-2 Primary Vaccination - The Journal of In

Mary Wilson

Well-known member
Published: 21 May 2023​

https://doi.org/10.1093/infdis/jiad163

Louis Fries, Neil Formica, Raburn M Mallory, Haixia Zhou, Joyce S Plested, Raj Kalkeri, Ioana Moldovan, Nita Patel, Gary Albert, Michelle Robinson ...Show more
Abstract

Background
NVX-CoV2373 is an efficacious COVID-19 vaccine comprising full-length 5-µg recombinant SARS-CoV-2 spike (rS) glycoprotein and Matrix-M™ adjuvant. Phase 2 of a randomized, placebo-controlled, phase 1/2 trial in healthy adults (18-84 years) previously reported good safety/tolerability and robust humoral immunogenicity.

Methods
Participants were randomized to placebo or 1 or 2 doses of 5-µg or 25-µg rS with 50 µg Matrix-M adjuvant 21 days apart. CD4+ T-cell responses to SARS-CoV-2 intact S or pooled peptide stimulation (with ancestral or variant S sequences) were measured via enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICCS).

Results
A clearly discernable spike antigen-specific CD4+ T-cell response was induced after 1 dose, but markedly enhanced after 2 doses. Counts and fold-increases in cells producing Th1 cytokines exceeded those secreting Th2 cytokines, although both phenotypes were clearly present. Interferon-γ responses to rS were detected in 93.5% of 2-dose 5-µg recipients. A polyfunctional CD4+ T-cell response was cross-reactive and of equivalent magnitude to all tested variants, including Omicron BA.1/BA.5.

Conclusions
NVX-CoV2373 elicits a moderately Th1-biased CD4+ T-cell response that is cross-reactive with ancestral and variant S proteins after 2 doses.

https://watermark.silverchair.com/j...0T-MbEalqpOrcbvUr2V2ecegU6x9yceMRDnJYjsL2cpzg
 
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