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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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 3

Spike-specific CD8+ T cells are induced following NVX-CoV2373 vaccination.

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Spike-specific CD8+ T cells are induced following NVX-CoV2373 vaccinatio...
(A) Representative FACS plots of AIM+ (CD69+4-1BB+) CD8+ T cells on day 0 (D0), D7, and D28 after vaccination. (B and C) Spike-specific AIM+ CD8+ T cells responses in vaccinees (black dots), placebo controls (gray dots), and convalescent COVID-19 donors (blue dots). (D) Representative FACS plots of IFN-γ responses in total spike-specific CD8+ T cells. IFN-γ+ (E), TNF-α+ (F), and IL-2+ (G) spike-specific CD8+ T cell responses in vaccinees, placebo controls, and convalescent COVID-19 controls. (H) Secreted-effector+ spike-specific CD8+ T cells (sum of CD8+ T cells expressing any combination of IFN-γ, TNF-α, IL-2, or GzmB, excluding GzmB single positives). (I) Pie charts depicting the proportion of spike-specific CD8+ T cells exhibiting 1, 2, 3, or 4 functions on day 7 and day 28 after immunization. Functionality was defined as a cell expressing any combination of IFN-γ, TNF-α, IL-2, or GzmB, excluding GzmB single positives. Dotted line indicates limit of sensitivity for the assay, and was calculated as the geometric mean of all sample DMSO wells multiplied by the geometric SD factor. 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.