Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

摘要: Genetic variability in Plasmodium falciparum malaria parasites hampers current vaccine development efforts. Here, we hypothesize that to address the impact of genetic on efficacy clinical trials, conserved antigen targets should be selected achieve robust host immunity across multiple strains. Therefore, suitable antigens assessed for levels polymorphism and diversity. Using a total one hundred two isolates from region high transmission Uganda, analyzed extent diversity four recently reported novel blood-stage candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal (PfGAMA), rhoptry-associated leucine zipper-like 1 (PfRALP1) Duffy binding-like merozoite surface (PfMSPDBL1). In addition, utilizing wheat germ cell-free system, expressed recombinant proteins candidates based P. laboratory strain 3D7 sequences, immunized rabbits obtain specific antibodies (Abs) performed functional growth inhibition assay (GIA). The GIA activity raised Abs was demonstrated using both homologous heterologous FVO strains vitro. Both pfripr pfralp1 are less polymorphic but latter is comparatively more diverse, with varied number regions having insertions deletions, asparagine 6-mer repeats coding sequences. Pfgama pfmspdbl1 genetically diverse among against 3D7-based PfGAMA PfMSPDBL1 inhibiting invasion only not strain. Moreover, although PfRipr PfRALP1 potently inhibited FVO, anti-PfRipr much higher than anti-PfRALP1. Thus, regarded as promising next-generation vaccines falciparum.