Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination
Author:
Fries Louis1, Formica Neil1, Mallory Raburn M1, Zhou Haixia2, Plested Joyce S3, Kalkeri Raj3, Moldovan Ioana4, Patel Nita2, Albert Gary5, Robinson Michelle6, Cho Iksung7, Chau Gordon7, Dubovsky Filip1, Glenn Gregory M2, Adams Mark, Arya Mark, Athan Eugene, Berger Ira, Bradley Paul, Glover Richard, Griffin Paul, Kim Joshua, Kitchener Scott, Klein Terry, Leah Amber, Lemech Charlotte, Lickliter Jason, Manning Mary Beth, Napier-Flood Fiona, Nugent Paul, Thackwray Susan, Turner Mark,
Affiliation:
1. Clinical Development 2. Discovery 3. Clinical Immunology, Novavax, Inc , Gaithersburg, Maryland 4. Cellular Technology Ltd , Shaker Heights, Ohio 5. Medical Writing 6. Clinical Operations 7. Biostatistics, Novavax, Inc , Gaithersburg, Maryland
Abstract
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.
Funder
Coalition for Epidemic Preparedness Innovations
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Immunology and Allergy
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