Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis

Abstract

Background Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population.Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analysed with 2200 global pfcsp sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of pfcsp showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko pfcsp gene had no obvious deviation from African mainland pfcsp (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global pfcsp C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of pfcsp were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

Genetic Diversity and Natural Selection on the Thrombospondin-Related Adhesive Protein (TRAP) Gene of Plasmodium Falciparum on Bioko Island, Equatorial Guinea and Global Comparative Analysis

“…Overall, with the polymorphism analysis, Bioko PfTRAP exhibited the high polymorphism, which is consistent with PfTRAP from other African countries but signi cantly distinct with the relatively low polymorphic Asian PfTRAP. These phenomena consistence with our previous report about Plasmodium falciparum circumsporozoite protein (PfCSP) gene [28], which also indicated that the similar polymorphic pattern between Bioko and Africa mainland countries. Moreover, our team had carried out the exploration and analysis of other vaccine candidate genes previously, including pre-erythrocytic stage CSP gene, erythrocytic phase merozoite surface protein (MSP-1/2) and asexual blood stage apical membrane antigen-1 (AMA-1) gene [28][29][30].…”

“…These phenomena consistence with our previous report about Plasmodium falciparum circumsporozoite protein (PfCSP) gene [28], which also indicated that the similar polymorphic pattern between Bioko and Africa mainland countries. Moreover, our team had carried out the exploration and analysis of other vaccine candidate genes previously, including pre-erythrocytic stage CSP gene, erythrocytic phase merozoite surface protein (MSP-1/2) and asexual blood stage apical membrane antigen-1 (AMA-1) gene [28][29][30]. These results shown that the polymorphism of candidate genes associated with malaria vaccines in Africa has been at a high level for a long time.…”