Compartmentalised mucosal and blood immunity to SARS-CoV-2 associated with high seroprevalence before Delta wave in Africa

Background The reported number of SARS-CoV-2 cases and deaths are lower in Africa compared to many high-income countries. However, in African cohorts, detailed characterisation of SARS-CoV-2 mucosal and T cell immunity are limited. We assessed SARS-CoV-2-specific immune landscape in The Gambia pre-Delta variant in July 2021. Methods A cross-sectional assessment of SARS-CoV-2 immunity in 349 unvaccinated individuals from 52 Gambian households was performed between March - June 2021. SARS-CoV-2 spike (S) and nucleocapsid (N) specific binding antibodies were measured by ELISA, variant-specific serum neutralizing-antibodies (NAb) by viral pseudotype assays and nasal fluid IgA by mesoscale discovery assay. SARS-CoV-2 T-cell responses were evaluated using ELISpot assay. Results We show that adjusted seroprevalence of anti-Spike antibodies was 56.7% (95% confidence interval (CI) 49.0–64.0), which was lower in children < 5 years (26.2%, 13.9–43.8) and 5–17 years (46.4%, 36.2–56.7) compared to adults 18–49 years (78.4%, 68.8–85.8). In spike-seropositive individuals, NAb titres were highest to Alpha variant (median IC50 110), with 27% showing pre-existing Delta variant titres > 1:50. Whilst T-cell responses were significantly higher in spike-seropositive individuals, 34% of spike-seronegative showed reactivity to one or more T-cell antigen pools. Strong correlations within SARS-CoV-2 T-cell, mucosal IgA, and serum NAb responses was observed. Conclusion High SARS-CoV-2 seroprevalence in The-Gambia induced mucosal and blood immunity, reducing Delta and Omicron impact. Children were relatively protected from infection. T-cell responses in seronegative individuals may indicate either pre-pandemic cross-reactivity or individuals with a T-cell dominated response to SARS-CoV-2 infection with absent or poor humoral responses.