Genetic analysis of the circumsporozoite gene in Plasmodium falciparum isolates from Cameroon: Implications for efficacy and deployment of RTS,S/AS01 vaccine

• Published in: Gene 2024-11, Vol.927, p.148744, Article 148744
• Main Authors: Kojom Foko, Loick Pradel, Hawadak, Joseph, Eboumbou Moukoko, Carole Else, Das, Aparup, Singh, Vineeta
• Format: Article
• Language: English
• Subjects: blood; Cameroon; Circumsporozoite protein; computer simulation; Diversity; DNA; genes; genetic analysis; genetic variation; haplotypes; malaria vaccines; Natural selection; Plasmodium falciparum; RTS,S/AS01 vaccine
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148744

[Display omitted] •Genetic diversity and evolution of P. falciparum circumsporozoite (Pfcsp) in Cameroon.•The central region of the Pfcsp gene was most genetically diverse.•Three and eight novel SNPs were found in N- and C-terminal regions, respectively.•The codon site 321 in the C-terminal region was under episodic positive selection.•The SNPs E357L, K322I, G349D, and D359Y) impact on function/structure. Current understanding of genetic polymorphisms and natural selection in Plasmodium falciparum circumsporozoite (PfCSP), the leading malaria vaccine, is crucial for the development of next-generation vaccines, and such data is lacking in Africa. Blood samples were collected among Plasmodium-infected individuals living in four Cameroonian areas (Douala, Maroua, Mayo-Oulo, Pette). DNA samples were amplified using nested PCR protocols, sequenced, and BLASTed. Single nucleotide polymorphisms (SNPs) were analysed in each PfCSP region, and their impact on PfCSP function/structure was predicted in silico. The N-terminal region showed a limited polymorphism with four haplotypes, and three novel SNPs (N68Y, R87W, K93E) were found. Thirty-five haplotypes were identified in the central region, with several variants (e.g., NVNP and KANP). The C-terminal region was also highly diverse, with 25 haplotypes and eight novel SNPs (N290D, N308I, S312G, K317A, V344I, D356E, E357L, D359Y). Most polymorphic codon sites were mainly observed in the Th2R subregion in isolates from Douala and Pette. The codon site 321 was under episodic positive selection. One novel (E357L) and three known (K322I, G349D, D359Y) SNPs show an impact on function/structure. This study showed extensive genetic diversity with geographical patterns and evidence of the selection of Cameroonian PfCSP central and C-terminal regions.