Novel hypervariable erythrocyte surface expressed recombinant proteins show promise as serological markers of exposure to Plasmodium falciparum infection

Abstract

Malaria caused by Plasmodium spp. leads to significant morbidity and mortality, particularly in Sub-Saharan African countries with Plasmodium falciparum being the predominant infectious species. The pathogenesis of P. falciparum depends on multiple host and parasitic factors, one of which is the evasion of host immune response due to antigenic variability during the blood stage of infection. The understudied infected erythrocyte expressed protein families STEVOR and RIFIN characterize with antigenic hypervariability and are associated with clinical outcome of the infection and protective acquired immunity based on their topology and localization. We have used two molecular tag methods for successful expression of members of STEVOR and RIFIN protein families as recombinant proteins in E. coli expression system. We have further established the antigenicity of those recombinants and have used Ugandan cohort samples with various P. falciparum infectious status and have compared the seropositivity rate to those recombinants in different age groups against already established short- and long-term markers of infection. We have demonstrated age-dependent immunity acquisition against the tested recombinants, and we have suggested the potential use of STEVOR and RIFIN recombinants as novel markers of P. falciparum infection in serosurveillance. Due to the hypervariability of those protein members we propose that further, more extensive research using a library of expressed variants is needed to strengthen the conclusions made in this study.