Background: Malaria remains a major public health burden in Cameroon, and the RTS,S/AS01E vaccine represents the first vaccine-based strategy targeting the circumsporozoite protein (CSP) of Plasmodium falciparum. While total IgG responses following vaccination are well documented, limited evidence exists regarding the functional distribution of IgG subclasses. This study evaluated anti-CSP IgG subclass responses in children aged 6–12 months vaccinated in three regions of Cameroon.
Methods: A longitudinal observational study was conducted among 208 children who received the three-dose RTS,S/AS01E vaccination schedule in three regions of Cameroon: the Center (Soa and Mfou District Hospitals), Littoral (Edea Regional Hospital and Japoma District Hospital), and West regions (Foumban and Foumbot District Hospitals) between October 2024 and November 2025. Blood samples collected at Visits 1, 2, and 3 were analyzed for IgG1, IgG2, IgG3, and IgG4 using ELISA. Malaria parasitaemia was assessed by light microscopy. IgG subclass seroprevalence and titers were compared across visits, regions, and parasitaemia status. Correlation analyses were performed to assess associations between antibody responses and parasite density.
Results: Vaccination induced a strong IgG subclass response predominantly characterized by IgG3, followed by IgG2 and IgG4, while IgG1 was the least produced subclass. Antibody titers increased significantly across vaccine doses, demonstrating a clear booster effect by Visit 3. Regional variations were observed, particularly in IgG3 levels. Parasitaemia influenced antibody responses, with higher IgG3 titers detected in parasitaemia-positive children at Visit 3 and an inverse correlation between IgG subclass titers and parasite density.
Conclusion: The RTS,S/AS01E vaccine induces a robust, dose-dependent anti-CSP IgG subclass response in young children, predominantly driven by IgG3. Regional and parasitaemia-related variations highlight the influence of local epidemiological factors on vaccine-induced immunogenicity. These findings provide important evidence supporting the implementation and immunological monitoring of malaria vaccination strategies in Cameroon and demonstrate the capacity of the vaccine to elicit a strong and functional immune response.
Keywords: IgG subclasses; RTS,S/AS01E; Plasmodium falciparum; malaria vaccine;