Abstract
The PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.
Highlights
The PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target
This study shows that field isolates of P. falciparum exhibit similar levels of invasion inhibition as lab and cultureadapted isolates when presented with varying levels of anti-BSG monoclonal antibody, supporting the hypothesis that the PfRh5-BSG invasion pathway is essential in field parasite populations and that there is minimal phenotypic variation in utilization of this pathway
We have shown the presence of the C203Y SNP, a SNP which is present at the PfRh5-BSG interface and is predicted to interact with the D2 of basigin[14], does not have a significant impact on the parasites’ dependence on the PfRh5-BSG invasion pathway, as measured by inhibition with MEM-M6/6, in these ex vivo associative studies
Summary
The PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. Vaccine-induced anti-PfRh5 antibodies from Aotus monkeys have been shown to be protective in a strain-transcendent manner in in vitro growth inhibition assays (GIA) and when naturally challenged with heterologous parasite g enotypes[5,6]. D assays have been shown to be a true mechanistic correlate of protection and so these assays, performed ex vivo with naturally occurring isolate populations, will be incredibly informative as to the degree of genotypic and phenotypic variation in the PfRh5-BSG pathway[12]. We investigate genotype–phenotype association studies ex vivo in a highly endemic region of Senegal to determine whether specific polymorphisms can influence the inhibition of monoclonal antibodies (mAbs) targeting the PfRh5-BSG invasion pathway
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