Evaluation of naturally acquired immune responses against novel pre-erythrocytic P. vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin

Abstract

Abstract Background Plasmodium vivax (Pv) represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing Pv vaccines as it would prevent disease and transmission. Here, we explore naturally acquired immunity to a panel of Pv PE antigens which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. Methods Twelve Pv PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and ELISpot. We used samples from Pv infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin. Results In our clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58–99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although titers persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). A significant correlation between IgG antibodies and the number of previous malaria episodes was observed only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). We observed a positive T cell response in 35% vs 9–35% of total volunteers against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. Conclusions Our results demonstrate clear humoral and T cell responses against Pv PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in Pv endemic areas.