Genetic diversity of the Plasmodium falciparum Pfs230 gene in four East African countries supports its potential as a malaria transmission‑blocking vaccine candidate

Abstract

The current wide-spread drug and insecticide resistance in malaria parasites and mosquito vectors reinforces the urgent need of innovative interventions such as stage-specific vaccines. Transmission-blocking vaccine (TBV) candidates, including Plasmodium falciparum Pfs48/45 and Pfs230 play an essential role in enabling parasite fertilization within mosquitoes. This study evaluated the genetic diversity and evolutionary dynamics of the Pfs230 gene to provide critical information on its potential as a suitable TBV candidate. The study utilized genomic data from the MalariaGEN Pf7 database, which included samples collected from four East African countries: Ethiopia, Kenya, Tanzania, and Uganda. Genetic metrics including nucleotide diversity, haplotype diversity (Hd), Tajima’s D, and Wright’s fixation index (FST) were computed to characterize the genetic diversity of the Pfs230 gene. Of the 1471 sequences retrieved, 1312 passed quality filtering and were retained for downstream analysis. Overall, nucleotide diversity of the Pfs230 gene was low across the four countries (π = 5.9 × 10-4). The Hd was 0.999 with 496 haplotypes among 718 monoclonal sequences, and 8.1% (n = 40) of the haplotypes were shared between two or more populations. The overall non-synonymous to synonymous substitution ratio was 0.43, and the Tajima’s D values were negative in all countries, with statistically significant lower values in Kenya (− 2.131; P < 0.01) and Tanzania (− 2.056; P < 0.05), while Ethiopia (− 0.972; P > 0.10) and Uganda (− 0.096; P > 0.10) had relatively higher values. Principal component analysis (PCA) and Wright's fixation index (FST) did not show any population differentiation. Similarly, the phylogenetic analysis indicated limited sequence divergence among populations. Low levels of genetic diversity and differentiation in the parasite populations was observed across the four countries suggesting that the Pfs230 gene is highly conserved, supporting its potential as a promising TBV candidate. Future studies focusing on Pfs230, alongside other key TBV targets will be essential for strengthening evidence-based needs to prioritize and incorporate this gene in the search for malaria vaccines with a broader protection against different parasite stages.