Background Malaria antigen-specific antibodies and polymorphisms in host receptors involved in antibody functionality have been associated with different outcomes of Plasmodium falciparum infections. Thus, to identify key prospective malaria antigens for vaccine development, there is the need to evaluate the associations between malaria antibodies and antibody dependent host factors with more rigorous statistical methods. In this study, we employ suitable statistical models to evaluate the predictive performance of malaria-specific antibodies and host gene polymorphisms on P. falciparum infection in a longitudinal cohort study involving Ghanaian children.
Methods Models with different functional forms were built using known predictors (age, sickle cell status, blood group status, parasite density, and mosquito bed net use) and malaria antigen-specific antibodies and FCGR3B polymorphisms shown to mediate antibody-dependent neutrophil function. The models were evaluated through visualization and assessment of differences between the Area Under the Receiver Operating Characteristic Curve and Brier Score estimated by suitable internal cross-validation designs.
Results This study has found that the FCGR3B-c.233C>A genotype and IgG against AMA1 were relatively better compared to the other antibodies and FCGR3B genotypes in classifying or predicting malaria risk among children.
Conclusions Apical Membrane Antigen 1 could be a key potential vaccine antigen while FCGR3B-c.233C>A under the additive and dominant models of inheritance could be an important modifier of the effect of malaria protective antibodies.