Longitudinal population analysis of Plasmodium falciparum apical membrane antigen-1 in Indian field isolates.

High genetic diversity is a major impediment to developing a universal malaria vaccine based on Plasmodium falciparum apical membrane antigen-1 (Pfama-1). Vaccine effectiveness against heterologous forms of the antigen requires information about existing genetic diversity of gene in circulation. Genotyping of Pfama-1 was performed on 147 archival samples from 14 different Indian states collected from 1993 to 2021. Genetic diversity and natural selection were assessed to explore the longitudinal variation in Pfama-1 in Indian P. falciparum field isolates. A total of 52 polymorphic sites were observed giving rise to 70 different haplotypes. Two novel amino acid substitutions S498C/G and F505Y, were observed in our samples. Highest genetic polymorphism was observed in Domain I (π = 0.025), while Domain II (π = 0.006) appeared to be most conserved across all states over the time. Non-significant positive Tajima D value (Taj D = 0.945, p > 0.10) was observed indicating that Indian Pfama-1 is under balancing natural selection. Although haplotype network was complex, structure analysis has shown no evidence of distinct genetic pattern state wise or change in Pfama-1 structure in time. Genetic structure of Pfama-1 in Indian field isolates is complex, exhibiting a high degree of genetic polymorphism. Since allele specific immunity is observed in the gene, Domain II which shows relative conservation across all states and between old and recent field isolates could have implications in vaccine design.