Plasmodium falciparum circumsporozoite protein: epidemiological variations among field isolates prevalent in India

Abstract

To investigate the extent of genetic variations in T-helper-cell epitopic regions of circumsporozoite (CS) protein in Plasmodium falciparum field isolates collected from different regions of India at different phases of malaria transmission. Genomic DNA was isolated from 507 P. falciparum wild-parasite isolates obtained from six geographical locations of India at three time points coinciding with malaria transmissions. The T-helper-cell epitopic regions were polymerase chain reaction (PCR)-amplified and the products were purified and then sequenced. Based on sequences, nine variants were found among isolates and they were categorized into nine groups (V-1 to V-9), where V-1 and V-2 were observed in all three time points (TP). The variants V-1 to V-4 in TP-1; V-1, V-2, V-5 to V-8 in TP-2; and V-1, V-2, V-5 and V-9 in TP-3 were present and they showed restricted heterogeneity. During peak transmission (TP-2), parasite populations were more diverse and heterogeneous and the variants regionally unbiased and restricted. However, the alleles of V-6 and V-9 in both Th2R and Th3R showed identical sequence variation with those observed in other geographical regions of the world. The remaining seven groups did not show such similarity. The Th2R and Th3R epitopes are implicated in host immune response to P. falciparum. The polymorphism in these epitopic regions indicates antigenic diversity, which may cause adverse outcome of a subunit vaccine including the CS prototype variant. Therefore, the formulation of a vaccine considering the restricted local repertoire parasite populations may be helpful.