Association between antibody responses to blood stage parasitic antigens and protection from Plasmodium falciparum and Plasmodium vivax Malaria in Timika, Indonesia

Abstract

Malaria is a major health problem causing over 212 million clinical cases every year around the world. In Indonesia, Timika is one of the highest malaria-endemic areas with a high annual parasite incidence (876 per 1,000 people per year) and high co-endemicity of P. falciparum as well as P. vivax. Moreover, a high rate of antimalarial drug resistance has also been reported in Timika, illustrating the need for developing other therapeutic tools such as vaccines to prevent disease.

Clinical immunity to malaria only develops after many years of constant exposure to the parasites. This form of protection does not result in sterilising immunity but prevents clinical cases by significantly reducing parasite density. Naturally acquired immunity predominantly targets blood- stage parasites and is known to require antibody responses, but despite the key role that antibodies play in protection the antigenic targets of immunity are not completely defined.

The aim of this study was to investigate associations between antibody responses and protection from symptomatic malaria in a field study conducted in Timika to identify targets of naturally acquired immunity to malaria. Naturally acquired immunity to seven Plasmodium falciparum and one Plasmodium vivax merozoite-stage vaccine candidate antigens were analyzed by ELISA, parasite growth inhibition functional assays (GIA) and ELISPOT. The main findings revealed that high antibody levels to P. vivax Duffy binding protein (PvDBP) were associated with high parasitemia. This finding suggests that PvDBP could be used as a serological marker for recent exposure. In contrast, high antibody responses to P. falciparum erythrocyte antigen 175 (PfEBA-175) Region IV-V, P. falciparum reticulocyte binding protein-like homologue 4 (PfRh4), PfRh5 and P. falciparum Rh5 interacting protein (PfRipr) predict protection from symtomatic malaria. Furthermore, PfRh5-specific memory B cells could be detected among protected malaria-exposed healthy controls as well as asymptomatic individuals, suggesting a role for these cells in sustaining long-term immunity. Together, these findings highlight that PfEBA-175, PfRh4, PfRh5, and PfRipr are important targets of naturally acquired immunity to malaria and promising vaccine candidates.