Genetic Diversity of Plasmodium vivax Cysteine-Rich Protective Antigen (PvCyRPA) in Field Isolates from Five Different Areas of the Brazilian Amazon

Abstract

The Plasmodium vivax Cysteine-Rich Protective Antigen (PvCyRPA) has an important role in erythrocyte invasion and has been considered a target for vivax malaria vaccine development. Nonetheless, its genetic diversity remains uncharted in Brazilian malaria-endemic areas. Therefore, we investigated the pvcyrpa genetic polymorphism in 98 field isolates from the Brazilian Amazon and its impact on the antigenicity of predicted B-cell epitopes. Genetic diversity parameters, population genetic analysis, neutrality test and the median-joining network were analyzed, and the potential amino acid polymorphism participation in B-cell epitopes was investigated. One synonymous and 26 non-synonymous substitutions defined fifty haplotypes. The nucleotide diversity and Tajima’s D values varied across the coding gene. The exon-1 sequence had greater diversity than those of exon-2. Concerning the prediction analysis, seven sequences were predicted as linear B cell epitopes, the majority contained in conformational epitopes. Moreover, important amino acid polymorphism was detected in regions predicted to contain residues participating in B-cell epitopes. Our data suggest that the pvcyrpa gene presents a moderate polymorphism in the studied isolates and such polymorphisms alter amino acid sequences contained in potential B cell epitopes, an important observation considering the antigen potentiality as a vaccine candidate to cover distinct P. vivax endemic areas worldwide.

Construction, Expression, and Evaluation of the Naturally Acquired Humoral Immune Response against Plasmodium vivax RMC-1, a Multistage Chimeric Protein

“…In this study, we focused on the third goal and described the construction and expression of a chimeric protein, PvRMC-1, designed based on our previous works that described B-cell epitopes in conserved regions of PvCyRPA, PvCelTOS, and Pvs25. We also evaluated the acquired antibodies against this protein in a population naturally exposed to malaria in the Brazilian Amazon First, in the design of PvRMC-1, we selected the full sequence of PvCyRPA after the signal peptide (255 amino acids) due to its small size and the moderate polymorphism found among field isolates in our previous work [34]. The two linear epitopes selected from Pvs25 were included as the main linear B-cell epitopes in strongly conserved regions of P. vivax isolates from endemic regions of the Americas and Asia [42,52,53].…”

“…A study measuring IgG antibodies to 38 P. vivax antigens indicated that CyRPA was the protein that needed less antibody titration to be related to protection [33], reinforcing the important role of this potential vaccine candidate. In addition, our group also explored this protein and PvCyRPA, and despite the moderate sequence variation, the potential antibody targets did not seem to be significantly affected [34].…”

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model

“…Despite basigin not being essential for P. vivax invasion, CyRPA remains crucial, and antibody responses to it correlate strongly with protection ( 24 ). PvCyRPA, despite moderate sequence variation, retains significant antibody targets ( 17 ). Regarding transmission, Pvs25 is expressed in mosquito stages with minimal genetic variation ( 18 ).…”