Antibodies to the repetitive epitope of Plasmodium falciparum circumsporozoite protein in a rural Tanzanian community: a longitudinal study of 132 children

Abstract

An ELISA employing a novel synthetic peptide consisting of 40 (Asn-Ala-Asn-Pro) repeats of Plasmodium falciparum circumsporozoite protein, (NANP)40, was used to detect antibodies against P. falciparum circumsporozoite protein in 132 children, 1 month to 15 years old, from a rural community (Kikwawila village) of Tanzania, a region where malaria is hyperendemic. The children were surveyed comprehensively over 3 consecutive years for clinical, parasitological, and serological parameters. Entomological data were also gathered for selected households in this village. The following results were obtained: anti-(NANP)40 antibodies increased as a function of age; the majority of children over 10 years showed a stable positivity for such antibodies during the longitudinal study; a negative correlation was observed between the levels of anti-sporozoite antibodies and both spleen enlargement and the presence of parasites in thick smears; no relationship was found between anti-(NANP)40 antibodies and asexual blood stage antibodies; children living in two representative households with comparable indoor resting mosquito densities showed markedly different frequencies of anti-(NANP)40 antibodies, in spite of comparable clinical, parasitological, and serological parameters. Thus, in addition to the exposure to infectious mosquito bites, other (e.g., genetic) factors, may play a role in the ability of certain individuals to mount an antibody response against this immunodominant repetitive epitope. The results presented in this paper confirm that the (NANP)40-ELISA represents a simple, reliable means for the detection of anti-(NANP)40 circumsporozoite protein antibodies and suggest that such antibodies may contribute to the immune protection against malaria in humans.