Cross-reactivity of rPvs48/45, a recombinantPlasmodium vivaxprotein, with sera fromPlasmodium falciparumendemic areas of Africa

Abstract

AbstractBackgroundPs48/45, aPlasmodiumgametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinantP. vivax Ps48/45 protein (rPvs48/45) with sera fromP. falciparum-exposed African donors.MethodsrPvs48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria – In addition, BALB/c mice were immunized with the rPvs48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract ofP. falciparumNF-54 gametocytes to evaluate the parasite-boosting effect on rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African sera was used to evaluate theex vivoTB activity onP. falciparum,using standard mosquito membrane feeding assays (SMFA).ResultsrPvs48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults (≥ 17 years) than young children (≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice withP. falciparumgametocytes boosted anti-Pvs48/45 antibody responses, recognizingP. falciparumgametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% againstP. falciparumin SMFA.ConclusionAfrican sera (exposed only toP. falciparum)cross-recognized the rPvs48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of aP. vivaxandP. falciparumcross-protective TB vaccine.