Genetic Polymorphism and Natural Selection of Apical Membrane Antigen-1 in Isolates from Vietnam

Apical membrane antigen-1 of (PfAMA-1) is a leading malaria vaccine candidate antigen. However, the genetic diversity of and associated antigenic variation in global field isolates are major hurdles to the design of an efficacious vaccine formulated with this antigen. Here, we analyzed the genetic structure and the natural selection of in the population of Vietnam. A total of 37 distinct haplotypes were found in 131 Vietnamese isolates. Most amino acid changes detected in Vietnamese were localized in the ectodomain, domains I, II, and III. Overall patterns of major amino acid changes in Vietnamese were similar to those of global , but the frequencies of the amino acid changes slightly differed by country. Novel amino acid changes were also identified in Vietnamese . Vietnamese revealed relatively lower genetic diversity than currently analyzed in other geographical regions, and suggested a distinct genetic differentiation pattern. Evidence for natural selection was detected in Vietnamese , but it showed purifying selection unlike the global analyzed so far. Recombination events were also found in Vietnamese . Major amino acid changes that were commonly identified in global were mainly localized to predicted B-cell epitopes, RBC-binding sites, and IUR regions. These results provide important information for understanding the genetic nature of the Vietnamese population, and have significant implications for the design of a vaccine based on PfAMA-1.