Limited genetic variations of the Rh5-CyRPA-Ripr invasion complex in parasite population in selected malaria-endemic regions, Kenya.

The invasion of human erythrocytes by merozoites requires interaction between parasite ligands and host receptors. Interaction of Rh5-CyRPA-Ripr protein complex with basigin, an erythrocyte surface receptor, is essential for erythrocyte invasion. Antibodies raised against each antigen component of the complex have demonstrated erythrocyte invasion inhibition, making these proteins potential blood-stage vaccine candidates. Genetic polymorphisms present a significant challenge in developing efficacious vaccines, leading to variant-specific immune responses. This study investigated the genetic variations of the Rh5 complex proteins in isolates from Lake Victoria islands, Western Kenya. Here, twenty-nine microscopically confirmed field samples collected from islands in Lake Victoria between July 2014 and July 2016 were genotyped by whole genome sequencing, and results compared to sequences mined from the GenBank database, from a study conducted in Kilifi, as well as other sequences from the MalariaGEN repository. We analyzed the frequency of polymorphisms in the Rh5 protein complex proteins, Rh5, CyRPA, Ripr, and P113, and their location mapped on the 3D protein complex structure. We identified a total of 58 variants in the Rh5 protein complex. Rh5 protein was the most polymorphic with 30 SNPs, while CyRPA was relatively conserved with 3 SNPs. The minor allele frequency of the SNPs ranged between 1.9% and 21.2%. Ten high-frequency alleles (>5%) were observed in Rh5 at codons 147, 148, 277, 410, and 429 and in Ripr at codons 190, 255, 259, and 1003. A SNP was located in protein-protein interaction region C203Y and F292V of Rh5 and CyRPA, respectively. Put together, this study revealed low polymorphisms in the Rh5 invasion complex in the Lake Victoria parasite population. However, the two mutations identified on the protein interaction regions prompts for investigation on their impacts on parasite invasion process to support the consideration of Rh5 components as potential malaria vaccine candidates.