Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination
Year: 2023
Type: article
Abstract: BACKGROUND: NVX-CoV2373 is an efficacious coronavirus disease 2019 (COVID-19) vaccine comprising full-length recombinant severe acute respiratory syndrome coronavirus 2 (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 of age) 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 assay and intracellular cytokine staining. 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. CLINICAL TRIALS REGISTRATION: NCT04368988.
Authors: Louis Fries, Neil Formica, Raburn M Mallory, Haixia Zhou, Joyce S Plested, Raj Kalkeri, Ioana Moldovan, Nita Patel, Gary Albert, Michelle Robinson, Iksung Cho, Gordon Chau, Filip Dubovsky, Gregory M Glenn, for the 2019nCoV-101 Study Group, Mark Adams, Mark Arya, Eugene Athan, Ira Berger, Paul Bradley, Richard Glover, Paul Griffin, Joshua Kim, Scott Kitchener, Terry Klein, Amber Leah, Charlotte Lemech, Jason Lickliter, Mary Beth Manning, Fiona Napier-Flood, Paul Nugent, Susan Thackwray, Mark Turner
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,536
OpenAlex ID: W4377164028