Abstract: Abstract Background Plasmodium falciparum circumsporozoite surface protein (PfCSP) serves as a prime candidate for malaria vaccine; however, its substantial genetic diversity presents significant challenges in development of universal vaccines. This study investigated the genetic diversity and natural selection of the pfcsp in P. falciparum isolates from Vietnam. Comparative analysis of 836 global pfcsp sequences from different geographical regions was also performed. Methods Blood samples were obtained from individuals infected with P. falciparum in five malaria-endemic provinces in Central Vietnam from 2018 to 2022. The pfcsp gene was amplified, cloned, and sequenced, yielding 95 pfcsp sequences. Nucleotide diversity and natural selection of pfcsp were analysed by programs, such as DnaSP, MEGA6, and STRUCTURE. Results Both the N- and C-terminal non-repeating regions of Vietnam pfcsp showed limited genetic diversities; however, significant polymorphisms such as A98G and a 19-amino acid insertion were observed in the N-terminal region of Vietnam isolates, aligning with trends in global pfcsp populations. The C-terminal region of Vietnam and global pfcsp populations displayed notable polymorphisms, particularly within the Th2R and Th3R regions. The central repeat region demonstrated high polymorphism due to substantial size variations, predominantly influenced by the varying numbers and types of peptide repeat motifs found both in Vietnam and global populations. Conclusion These findings offer critical insights into the genetic composition of the global pfcsp population and provide useful information in designing effective vaccines based on PfCSP.
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