T-Cell Interferon Gamma Responses to SARS-CoV-2 Following Infection with/Without Vaccination in a Tanzanian Population

Abstract

Background: T-cell responses are crucial in SARS-CoV-2 immune-control; however, limited data exist from African populations. We assessed interferon-gamma (IFN-γ) release by T cells among Tanzanian adults (18-70 years) previously infected with or without SARS-CoV-2 vaccination, using the ELISpot assay. We also characterized background plasma IFN-γ levels in this population. Methods: Peripheral blood mononuclear cells (PBMCs) from 143 individuals, sampled 1-12 months post SARS-CoV-2 exposure, were stimulated with overlapping peptides spanning the Spike and Nucleocapsid proteins. T-cell responses were measured by ELISpot assay, and plasma IFN-γ concentrations by ELISA. Associations with participant characteristics were analyzed using gamma linear and modified Poisson regression models (p < 0.05 considered significant). Results: We found high background T-cell IFN-γ release in 73.4% (105/143) of participants, leaving 38 (26.6%) with detectable responses above background; (38/38;100%) to Spike and (36/38;94.7%) to Nucleocapsid peptides. T-cell response magnitude did not differ by symptomatic/asymptomatic infection or vaccination status. However, each one-year increase in age was associated with a 1% decline in mean T-cell response (p = 0.029). Moreover, among participants with high background responses, 43/105;41% had elevated plasma IFN-γ, and 5/105; 4.8% showed cytokine storm-level concentrations. Alcohol consumption was significantly associated with elevated plasma IFN-γ (p = 0.041). Conclusion: Strong and possibly cross-reactive T-cell responses to SARS-CoV-2 were detected in Tanzanian individuals following infection with/without vaccination. Moreover, high plasma IFN-γ levels were detected, especially among participants who consumed alcohol. We recommend for modifications of the ELISpot T-cell assays to optimize the evaluation of pathogen-specific T-cell responses among African residents given the high background IFN-γ release.