Genetic diversity of the malaria vaccine candidate PfRIPR in a high transmission region of Senegal

RH5-interacting protein (RIPR) is essential for the invasion of Plasmodium into host red blood cells and is currently being studied as a novel malaria vaccine candidate in Phase 1a clinical trials. To study the genetic diversity of RIPR, deep amplicon sequencing was used to identify RIPR mutations in Plasmodium falciparum clinical isolates (n = 89) collected in Kédougou, a high malaria transmission region of Senegal. We identified non-synonymous single-nucleotide polymorphisms (SNPs) in 64/89 (71.9%) of samples. In total, 26 non-synonymous SNPs were identified, including 15 novel SNPs. Sixteen of 26 SNPs could be threaded onto existing PfRIPR crystal structures to predict the effects of SNPs on RIPR stability. Seven of 16 mutations were predicted to destabilize PfRIPR, while two of 16 were predicted to increase the stability of RIPR. Additionally, we identified 3 SNPs (Q737K, T738K, and V840L) in the EGF5-8 domains of PfRIPR where neutralizing antibodies are known to bind.