Genetic polymorphism of circumsporozoite protein of Plasmodium falciparum isolates in children in Brazzaville, Republic of Congo

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BACKGROUND: The first WHO-approved malaria vaccines (RTS, S/AS01, and R21/Matrix M) target part of the Plasmodium falciparum circumsporozoite protein (PfCSP), displays a degree of polymorphism that may raise concerns about vaccine efficacy. As a prelude to vaccine implementation, the study here reports investigation on Pfcsp gene polymorphisms in isolates from Congolese individuals in the Republic of Congo. METHODS: Blood samples were collected from 202 children infected with P. falciparum during a cross-sectional study from March to October 2021. The full-length Pfcsp gene was amplified by nested PCR and sequenced using the Oxford Nanopore platform. RESULTS: Overall, 30 haplotypes were identified in the N-terminal region of the protein. The A98G mutation was the most frequent (25.6%), while KLKQP was the most conserved motif. In the central repeat region, 50 haplotypes were found, with a predominance of the NANP motif, although some haplotypes contained the NVDP, NEDP and NVNP variants. C-terminal region was highly polymorphic, with 76 haplotypes identified among the 174 sequenced samples. In the C-terminal Th2R region, the major mutations identified included K317E (87.4%) and N321K (83.9%), with a nucleotide diversity of π = 0.16. In the Th3R region, the E357Q (75.9%) mutation was predominant, with a nucleotide diversity of π = 0.08. Neutrality tests revealed contrasting patterns of evolution between the Th2R and Th3R regions. CONCLUSION: This study provides baseline data on Pfcsp genetic diversity in a defined area of the Republic of Congo. The results highlight the degree of variation in natural parasite populations at gene loci relevant to vaccine-targeted epitopes of (PfCSP) antigen. Further research incorporating immunological data will be needed to conduct in-depth assessments of vaccine efficacy.

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