Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination

• Published in: The Journal of infectious diseases Vol. 228; no. 6; pp. 734 - 741
• Main Authors: Fries, Louis, Formica, Neil, Mallory, Raburn M, Zhou, Haixia, Plested, Joyce S, Kalkeri, Raj, Moldovan, Ioana, Patel, Nita, Albert, Gary, Robinson, Michelle, Cho, Iksung, Chau, Gordon, Dubovsky, Filip, Glenn, Gregory M
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.09.2023
• Subjects: CD4 antigen; Clinical trials; Coronaviruses; COVID-19; Cytokines; Immunogenicity; Lymphocytes T; Major; Phenotypes; Placebos; Severe acute respiratory syndrome coronavirus 2; γ-Interferon; COVID-19 vaccine; CD4; variant cross-reactivity; polyfunctional; Matrix-M adjuvant; T-cell response
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiad163

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. Primary series of NVX-CoV2373 vaccine with Matrix-M adjuvant induces polyfunctional CD4+ T-cell responses of balanced to moderately Th1-biased phenotype. Essentially equivalent cytokine production by vaccinee cells can be stimulated by spike proteins of ancestral or multiple variant sequences.