Genetic diversity, natural selection, and immunological features of the Plasmodium vivax CyRPA protein: Implications for vaccine development.

Malaria caused by Plasmodium vivax remains a significant public health challenge, with vaccine development hindered by factors such as antigenic diversity and immune evasion. The Cysteine-Rich Protective Antigen (CyRPA), a key protein involved in erythrocyte invasion, has emerged as a promising vaccine candidate. However, its genetic diversity and immunological properties have not been fully explored. This study aimed to analyze the genetic diversity, selective pressures, and antigenic potential of the pvcyrpa locus using 950 sequences, including 42 newly obtained isolates from Colombia. The pvcyrpa gene displayed high nucleotide diversity shaped by both natural selection and recombination. In-silico predictions identified B- and T-cell epitopes, encompassing mainly polymorphic regions, with strong binding affinities predicted for multiple HLA alleles. Notably, these epitopes overlapped with regions previously shown to elicit immune responses in natural infections, as reported in a recent study. Moreover, immune simulation of a multiepitope C-terminal construct predicted a robust humoral memory profile. Collectively, these genetic, epitope-mapping, and immune-simulation findings highlight the conserved C-terminal region of PvCyRPA as a strong, broadly reactive vaccine candidate, providing a rational basis for subsequent in-vitro and in-vivo validation.