Adults in Ghana generate higher and more durable neutralising antibody titres following primary course COVID-19 vaccination than matched UK adults: The HERITAGE Study

Background: Little data exist on the COVID-19 vaccine response in African countries who despite having high disease burden, have low COVID-19 mortality rates. We investigated the longitudinal immune response in a West-African urban population upon COVID-19 vaccination, two years after the start of the pandemic. Methods: The HERITAGE study is a prospective cohort study of 301 residents of Accra, Ghana. Participants received two doses of a COVID-19 vaccine (AZD1222 or BNT162b2) from December 2021 and were followed-up for 12 months. COVID-19 status was determined by RT-PCR at seven time points. Serological responses, including anti-Nucleocapsid IgG, anti-Spike IgG and live-virus neutralisation were determined at four time points during the 12 months follow-up. Results: COVID-19 positivity was 19.3% at baseline and reduced rapidly upon vaccination. Serological analyses indicated previous exposure to SARS-CoV-2 in 80.5% of the HERITAGE participants. After vaccination, neutralising antibody titres (NAbTs) against six different SARS-CoV-2 variants significantly (p < 0.001) increased, with fold changes (FC) ranging from 1.87 to 4.59. Highest NAbTs were recorded in the previously exposed group. Participants without prior exposure showed a continues increase in NAbTs between months 3 and 12 for circulating variants (Omicron B.A2 (FC 2.44, p < 0.001) and XBB.1.5 (FC 1.91, p = 0.05)). By comparison a matched cohort from the UK-based LEGACY study showed generally lower NAbTs at baseline (HERITAGE vs LEGACY for Wild-type: 250.3 vs 141.3, p < 0.0001, for A.27 84.6 vs 43.2, p = 0.0129, for Eta 159.7 vs 118.1, p = 0.3428, for Delta 158.6 vs 10.0, p < 0.0001, for Omicron B.A2 153.7 vs 10.0, p < 0.0001) and after receiving the vaccine (HERITAGE vs LEGACY for Wild-type: 882.6 vs 337.7, p < 0.0001, for A.27 552.0 vs 227.7, p = 0.0001, for Eta 682.2 vs 295.3, p < 0.0001, for Delta 557.6 vs 165.1, p < 0.0001, for Omicron B.A2 283.3 vs 124.2, p < 0.0001). NAbTs kinetics between the two cohorts were more similar when analysis was restricted to previously unexposed participants when adjusted for circulating variants during the sampling period. Conclusions: Two doses of AZD1222 or BNT162b2 significantly increased existing NAbTs against SARS-CoV-2 in a highly exposed population, showing durable boosting of pre-existing infection-induced immunity. This indicates the importance of considering local population exposure in vaccination design and deployment.