Characterising protective immune responses to SARS-CoV-2 in urban and rural Malawi between February 2021 and April 2022

SARS-CoV-2 transmission in Malawi remains unclear due to high proportions of mild/asymptomatic infections and limited diagnostics. Existing seroprevalence studies in Malawi have primarily used convenience samples and enzyme-linked immunosorbent assays (ELISAs). We assessed SARS-CoV-2 neutralisation in a longitudinal Malawian population-based cohort, assessing protective immunity post-infection and vaccination. Sera were obtained from rural (Karonga, n = 958) and urban (Lilongwe, n = 918) based participants at three-monthly intervals (February 2021-April 2022). Neutralising antibodies against SARS-CoV-2 were measured using human immunodeficiency (HIV)-based pseudotype assays in HIV-uninfected participants, and vesicular stomatitis virus-based assays in HIV-infected participants and an HIV-uninfected subset. Nucleocapsid ELISAs identified vaccinated participants also infected. SARS-CoV-2 neutralisation profiles increased in complexity over time from rising vaccination coverage and emerging variants. Neutralising antibody prevalence was higher in Lilongwe than Karonga (68.1% (CI 63.5-72.4) vs. 45.4% (CI 41.6-49.3), Survey 4). Hybrid immune and solely vaccinated participants exhibited higher titres than those solely infected. Children < 15 years had the lowest neutralising antibody titres among infected (not vaccinated) participants. People living with HIV had lower neutralising responses than those HIV-uninfected, particularly post vaccination. We therefore recommend surveillance of children and people living with HIV as low neutralisation responses increase reinfection risk. COVID-19 vaccination should be prioritised for HIV-infected individuals.