Longitudinal Antibody Dynamics Following SARS-CoV-2 Viral-Vectored and mRNA Booster Vaccination in Ghanaian Adults

Background/objectives: SARS-CoV-2 antibodies wane after natural infections and vaccinations. COVID-19 booster vaccination enhances the durability and functionality of antibodies against emerging SARS-CoV-2 variants. Data on booster-induced antibody durability in sub-Saharan Africa remain sparse. Comparative analysis of vaccine-induced responses between heterologous and homologous vaccination regimens remains limited. This study evaluated longitudinal RBD-specific IgG responses following homologous and heterologous COVID-19 booster vaccination in previously vaccinated adults. Methods: Adults with prior mRNA or adenoviral-vectored vaccination were boosted with either Pfizer (mRNA) or Janssen (adenoviral-vectored) vaccines. Plasma IgG binding to Wuhan, Delta, and Omicron RBDs was measured pre-booster and at 3, 6, and 9 months. A total of 181 participants were enrolled between November 2022 and October 2023. Results: More than 60% of participants had detectable pre-booster RBD- and N-antigen-specific IgG. Booster vaccination substantially increased Wuhan-specific RBD-IgG at three months, with limited boosting of Delta and Omicron responses. Antibody levels waned to pre-booster concentrations by month nine. Heterologous boosting with a viral-vectored prime followed by Pfizer mRNA significantly enhanced both peak RBD-IgG levels and durability. Conclusions: These longitudinal data provide rare real-world evidence on booster immunogenicity in African adults and demonstrate that heterologous regimens confer a short- to intermediate-term advantage in antibody magnitude compared to a homologous regimen. This benefit was most pronounced within the first six months post-boost. The findings support additional booster dosing to strengthen protection against emerging variants in sub-Saharan Africa.