Genetic diversity and natural selection of cell-traversal protein for ookinetes and sporozoites (CelTOS) in Plasmodium falciparum isolates from Vietnam.

Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) plays a crucial role in the parasite's life cycle at both vector and human liver stages and is a potential vaccine candidate impacting various phases of the parasite's life cycle. However, current knowledge about the genetic diversity and evolutionary trend of this gene, which could impede the development of effective vaccines based on this protein, remains greatly limited. In this study, genetic diversity and natural selection in Vietnamese pfceltos were analyzed. Blood samples were collected from P. falciparum-infected malaria patients in three malaria-endemic provinces of Vietnam (Dak Lak, Gia Lai, and Phu Yen) between 2018 and 2022. A total of 366 pfceltos sequences were obtained from 366 Vietnamese P. falciparum isolates. Twenty-nine polymorphic amino acid changes were identified in the Vietnamese pfceltos. Four amino acid substitutions, K100N, S104L, F117V, and N119K, were commonly detected in Vietnam pfceltos populations. Although Vietnamese pfceltos sequences revealed a low genetic diversity, geographical differences were also found. Dak Lak pfceltos showed a greater genetic diversity than those from Gia Lai and Phu Yen, and displayed different population structure. This study highlights the limited genetic diversity of pfceltos in Vietnamese P. falciparum, with slight regional differences in genetic diversity and natural selection profiles identified. The relatively low genetic diversity and tight conservation of biologically significant amino acids in Vietnamese pfceltos sequences highlight PfCelTOS's potential as an attractive vaccine candidate; however, further genetic analysis of global pfceltos populations is essential to better understand the genetic basis of this vaccine candidate.