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

Abstract

Apical membrane antigen-1 of Plasmodium falciparum (PfAMA-1) is a leading malaria vaccine candidate antigen. However, the genetic diversity of pfama-1 and associated antigenic variation in global P. falciparum 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 pfama-1 in the P. falciparum population of Vietnam. A total of 37 distinct haplotypes were found in 131 P. falciparum Vietnamese isolates. Most amino acid changes detected in Vietnamese pfama-1 were localized in the ectodomain, domains I, II, and III. Overall patterns of major amino acid changes in Vietnamese pfama-1 were similar to those of global pfama-1, but the frequencies of the amino acid changes slightly differed by country. Novel amino acid changes were also identified in Vietnamese pfama-1. Vietnamese pfama-1 revealed relatively lower genetic diversity than currently analyzed pfama-1 in other geographical regions, and suggested a distinct genetic differentiation pattern. Evidence for natural selection was detected in Vietnamese pfama-1, but it showed purifying selection unlike the global pfama-1 analyzed so far. Recombination events were also found in Vietnamese pfama-1. Major amino acid changes that were commonly identified in global pfama-1 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 pfama-1 population, and have significant implications for the design of a vaccine based on PfAMA-1.

Genetic polymorphism and natural selection of the erythrocyte binding antigen 175 region II in Plasmodium falciparum populations from Myanmar and Vietnam

“…The reason why these two populations showed such distinct patterns of genetic differentiation and is currently unclear. Such different genetic profile of Vietnam P. falciparum population compared to the populations from other neighboring countries in the GMS, including Myanmar and Thailand, has been reported previously 18 . These findings may indicate that the distinctiveness of genetic composition of Vietnam P. falciparum was not limited to the pfeba-175 gene alone but encompasses the other genes in the Vietnam P. falciparum population.…”

Genetic Diversity of Circumsporozoite Surface Protein of Plasmodium vivax from the Central Highlands, Vietnam

“…Understanding the genetic structure of Plasmodium populations in the endemic areas will provide fundamental data for evaluating and improving efforts to control and eliminate malaria in Vietnam. However, limited information on the genetic make-up or structure of Vietnamese malaria parasites, both for P. falciparum and P. vivax , is currently available [ 35 , 36 , 37 , 38 , 39 , 40 ]. In this study, the genetic diversity and natural selection of pvcsp in Vietnamese P. vivax isolates collected in Central Highlands, Vietnam were analyzed to understand the genetic structure of the parasite and to provide expanded information in designing a vivax malaria vaccine based on PvCSP, a leading vaccine candidate.…”