Genetic analysis of the circumsporozoite gene in Plasmodium falciparum isolates from Cameroon: Implications for efficacy and deployment of RTS,S/AS01 vaccine.
Gene
; 927: 148744, 2024 Nov 15.
Article
de En
| MEDLINE
| ID: mdl-38964492
ABSTRACT
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Plasmodium falciparum
/
Haplotypes
/
Protéines de protozoaire
/
Paludisme à Plasmodium falciparum
/
Vaccins contre le paludisme
/
Polymorphisme de nucléotide simple
Limites:
Humans
Pays/Région comme sujet:
Africa
Langue:
En
Journal:
Gene
Année:
2024
Type de document:
Article
Pays d'affiliation:
Inde
Pays de publication:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS