NVX-CoV2373 vaccination induces functional SARS-CoV-2–specific CD4+ and CD8+ T cell responses
Carolyn Rydyznski Moderbacher, … , Gregory Glenn, Shane Crotty
Carolyn Rydyznski Moderbacher, … , Gregory Glenn, Shane Crotty
Published August 9, 2022
Citation Information: J Clin Invest. 2022;132(19):e160898. https://doi.org/10.1172/JCI160898.
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Research Article Immunology

NVX-CoV2373 vaccination induces functional SARS-CoV-2–specific CD4+ and CD8+ T cell responses

Abstract

NVX-CoV2373 is an adjuvanted recombinant full-length SARS-CoV-2 spike trimer protein vaccine demonstrated to be protective against COVID-19 in efficacy trials. Here we demonstrate that vaccinated individuals made CD4+ T cell responses after 1 and 2 doses of NVX-CoV2373, and a subset of individuals made CD8+ T cell responses. Characterization of the vaccine-elicited CD8+ T cells demonstrated IFN-γ production. Characterization of the vaccine-elicited CD4+ T cells revealed both circulating T follicular helper (cTfh) cells and Th1 cells (IFN-γ+, TNF-α+, and IL-2+) were detectable within 7 days of the primary immunization. Spike-specific CD4+ T cells were correlated with the magnitude of the later SARS-CoV-2–neutralizing antibody titers, indicating that robust generation of CD4+ T cells, capable of supporting humoral immune responses, may be a key characteristic of NVX-CoV2373 that utilizes Matrix-M adjuvant.

Authors

Carolyn Rydyznski Moderbacher, Christina Kim, Jose Mateus, Joyce Plested, Mingzhu Zhu, Shane Cloney-Clark, Daniela Weiskopf, Alessandro Sette, Louis Fries, Gregory Glenn, Shane Crotty

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Figure 2

Cytokine-producing spike-specific CD4+ T cell responses following NVX-CoV2373 vaccination.

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Cytokine-producing spike-specific CD4+ T cell responses following NVX-Co...
Proportion of (A) IFN-γ+, (B) TNF-α+, and (C) IL-2+ spike-specific CD4+ T cells detected following peptide stimulation. (D) Representative FACS plots and (E) proportion of IFN-γ+ intracellular CD40L+ (iCD40L+) responses in spike-specific CD4+ T cells on days 0, 7, and 28 after vaccination. (F) Proportion of spike-specific CD4+ T cells expressing iCD40L and producing IFN-γ, TNF-α, IL-2, or GzmB (“secreted-effector+”). Predominant multifunctional profiles of spike-specific CD4+ T cells with 1, 2, 3, 4, or 5 functions were analyzed on (G) day 0 (D0), (H) D7, and (I) D28 after vaccination. (J) Pie charts depicting the proportion of spike-specific CD4+ T cells exhibiting 2, 3, 4, or 5 functions on day 7 and day 28 after immunization. Functionality is defined as a cell expressing iCD40L and any combination of IFN-γ, TNF-α, IL-2, or GzmB. Dotted line indicates LOQ for the assay, and was calculated as the geometric mean of all sample DMSO wells multiplied by the geometric SD. Percentage responders was calculated as responses ≥ LOQ divided by the total samples in the group. Paired data were analyzed by Wilcoxon’s signed-rank test. Data shown as geometric mean ± geometric SD. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.