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Pre-COVID-19 ex vivo cross-reactive IFN-γ cellular response to SARS-CoV-2 spike overlapping peptides is more robust among Kenyan compared to Swedish adults

Wanjiku, p.; Orindi, B.; Mwacharo, J.; Chemweno, J.; Karanja, H.; Kronsteiner-Dobramysl, B.; Kai, O.; Wright, D.; Ochola-Oyier, L. I.; Sundling, C.; Dunachie, S.; Warimwe, G. M.; Farnert, A.; Bejon, P.; Ndungu, F. M.; Nduati, E.

2025-01-27 allergy and immunology
10.1101/2025.01.24.25321024 medRxiv
Show abstract

IntroductionGlobal WHO data indicate that Sub-Saharan African (SSA) countries, such as Kenya, experienced reduced coronavirus disease 2019 (COVID-19) severe-morbidity and mortality burdens relative to their more affluent counterparts in Europe, Asia, and North America. MethodsWe analysed peripheral blood mononuclear cells (PBMC) samples collected from Kenya and Sweden before and during COVID-19. Pre-COVID-19 samples were available for 80 adults and 10 infants from Kenya, and 20 adults from Sweden. COVID-19 samples were available for 39 Kenyan adults. The samples were analysed for ex vivo IFN-{gamma} secretion using an Enzyme-Linked Immunosorbent (ELISpot) assay following in vitro stimulations with overlapping SARS-CoV-2 spike-protein peptides. T-cells expressing IFN-{gamma}, IL-2, TNF-, CD154, and CD107a were assessed following similar stimulations, using intracellular cytokine staining (ICS) and multiparameter flow cytometry. Results55.7% of the Kenyan pre-COVID-19 adults were classified as responders by ELISPOT responses to spike-protein peptides, compared with 28% of Swedish pre-COVID-19 adults (p = 0.04). The frequencies for SARS-CoV-2 spike-specific TNF- CD4+, TNF- CD8+ and IFN-{gamma} CD8+ T-cell responses, tended to be higher in the Kenyan adults although these differences did not reach statistical significance. ConclusionPre-COVID-19 T-cell responses could contribute to lower morbidity and mortality associated with SARS-CoV-2 infections in SSA relative to Europe, Asia, and North America. HighlightsO_LIHigher frequencies of cross-reactive IFN-{gamma}-secreting cells among Kenyan pre-COVID-19 adults compared to Sweden. C_LIO_LITrends of higher TNF- and IFN-{gamma} T-cell responses among Kenyan adults. C_LIO_LIPresence of pre-existing T-cell immunity in Sub-Saharan Africa. C_LI

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