Pattern and association of immunoglobulin G antibodies to AMA1, GLURP, and MSP3 with protection from malaria in a cohort of Cameroonian children living in Mutengene: Anaemia a possible collateral damage?

Understanding the characteristics of naturally acquired immunity in different epidemiologic settings is essential for vaccine development and testing. The relationship between antibodies against four malaria vaccine candidate antigens and protection from malaria in a cohort of Cameroonian children was assessed. Immunoglobulin (Ig)G and IgG subclasses against recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1), glutamate rich protein (GLURP) R0, GLURP R2 and merozoite surface protein 3 (MSP3) in the plasma of 357 Cameroonian children were measured by sandwich ELISA at three time points (baseline, 6 months and 12 months) during which time participants were monitored for malaria.Total IgG to all four antigens correlated positively with age (0.51≤ r ≤ 0.23, p < 0.001) at all three time points. Adjusting for age, total IgG, IgG1, IgG3, IgG2 (except for MSP3 IgG2) antibody levels to all four antigens were associated with protection against malaria parasitaemia at baseline. GLURP R0 IgG (F = 35.7, p < 0.001), GLURP R2 IgG (F = 16.5, p < 0.001), AMA1-3D7 IgG2 (F = 10.8, p < 0.001) and AMA1-3D7 IgG3 (F = 4.01, p = 0.019) decreased with a corresponding decrease in malaria cases (χ ² = 10.4, p = 0.034) across the three time points, contrary to the increase observed in MSP3 IgG (F = 8.9, p < 0.001) and MSP3 IgG2 (F = 44.2, p < 0.001). Increased levels of AMA1-3D7 IgG [OR = 4.13, 95% CI (1.09 – 15.65), p = 0.037] and MSP3 IgG1 [OR = 8.16, 95% CI (1.06 – 62.64), p = 0.044] were associated with susceptibility to anaemia after controlling for age and parasitaemia.Total IgG, cytophilic subclasses and IgG2 to all the antigens (except MSP3 IgG2) were associated with malaria protection while MSP3 IgG seemed to persist longer. The relationship between malaria specific antibodies and anaemia warrants further studies.