Journal Article

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Villasante, Eileen, Wang, Gregory, Sanchez-Edwards, Margaret, Belmonte, Maria, Broder, Christopher C., Porter, Chad, Reyes, Anatolio E., Mitre, Edward, Goguet, Emilie, Alcorta, Yolanda, Ganeshan, Harini, Malloy, Allison M. W., Laing, Eric D., Sedegah, Martha, Acheampong, Neda, Illinik, Luca, Hollingdale, Michael R., Ramsey, Kathy F., Huang, Jun, Jackson-Thompson, Belinda, Inoue, Sandra, Maiolatesi, Santina E., Burgess, Timothy H., Hollis-Perry, Monique, Pollett, Simon D., Belmonte, Arnel

2022

Overview

Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination (‘hybrid immunity’) further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/10 6 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Antibodies / Antigens / Biology and Life Sciences / Cellular structure / Coronaviruses / COVID-19 / COVID-19 vaccines / Cytokines / Epitopes / Glycoproteins / Immune response / Immunity / Immunoglobulin G / Infections / Interferon / Interferon gamma / Interleukin 2 / Interleukins / Leukocytes (mononuclear) / Lymphocytes / Lymphocytes T / Medical personnel / Medicine and Health Sciences / mRNA / Peptides / Peripheral blood mononuclear cells / Proteins / Proteomes / Review boards / Severe acute respiratory syndrome coronavirus 2 / Structural proteins / Structure / Vaccination / Vaccines / γ-Interferon