Longitudinal Analysis of Plasmodium Falciparum Merozoite Antigenic Profilesand Antibody Profiles of Children With Multiple Malaria Episodes in Kilifi, Kenya

Abstract

Plasmodium falciparum, the main cause of malaria, has been implicated as a major driver of human evolution. To counter the deadly effects of malaria, the body mounts an immune response to the parasite. However, this response does not result in sterile immunity, an observation attributed to among other factors, the subversion of host immune cells, and variability of parasites infecting the host. This study, determines whetherparasites obtained from children with multiple malaria episodes are different genetically,and antigenically, with respect to Plasmodium falciparumReticulocyte binding like protein homologue 5 (PfRh5). The Rh5 gene, from a total of 422 Plasmodium DNAsamples takenfrom 34 children having sequential episodes of malaria,was sequenced to detect and identify polymorphisms within the infections. Contemporaneous plasma obtained from the infected children was tested for antibodies against recombinant proteins from 5 common Rh5 alleles by Enzyme Linked Immunosorbent Assay (ELISA), to determine if they would display allele-dominant reactivity. The sequencing data showed that most of theinfections contained more than one of the 5 common alleles. Consistent with other studies, the prevalence and levels of anti-PfRh5 antibodies were very low.Together,sequence and ELISA data showed that only 12 out of 92 episodes, which were allfrom variant YHK, showed allele-dominant reactivity. However, 50% of the 12 episodes were from one individual, which would warrant the use of more sensitive techniques to determine the true nature of these allele-dominant responses. Generally, this study suggests that there is little evidence of differential immune responses to the infecting genotype, thus lending weight to PfRh5 being an ideal vaccine candidate