Analysis of human antibodies to erythrocyte binding antigen 175 peptide 4 of Plasmodium falciparum

Background: The IgG1 and IgG3 antibodies are considered cytophilic and protective against Plasmodium falciparum, whereas IgG2 and IgG4 are thought to block protective mechanisms. Objectives: The main objective was to measure antibodies directed against erythrocyte binding antigen-175 (EBA-175) peptide 4 and analyze the relationship between such antibodies and clinical malaria attack. Methods: Using an enzyme-linked immunosorbent assay, a retrospective analysis of naturally acquired antibodies to synthetic peptide from EBA-175 peptide 4 has been carried out in 158 school children from the village of Dienga in Gabon. Results: The overall prevalence rates of antibodies to EBA-175 peptide 4 were 85.2%, 66.8%, 52.6%, 71.6% and 64.0% for total IgG, IgG1, IgG2, IgG3 and IgG4, respectively. Protection from clinical malaria, determined after a prospective 1-year study, was associated with the levels of IgG and IgG1 antibodies that increased with age. Conclusion: Together, these data suggest that age/exposure-related acquisition of anti-EBA-175 antibodies may contribute to the development of clinically protective immunity and could be taken into account in malaria control strategies when they are confirmed.