Abstract
BackgroundPlasmodium 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.MethodsFrom 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.ResultsIn 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).ConclusionsThe 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.
Highlights
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
Besides of RTS, S/AS01, a live attenuated Plasmodium falciparum whole sporozoite (SPZ) vaccine is regarded as a great potential malarial vaccine. Sanaria® PfSPZ Vaccine had conducted a clinical trial on Bioko Island where 70% vaccinees developed antibodies to P. falciparum circumsporozoite protein, which was the first clinical trial conducted in Equatorial Guinea [9]
Genetic polymorphisms of N‐terminal region of Bioko and global pfcsp The N-terminal non-repeat region was relatively conserved in Bioko pfcsp
Summary
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. Malaria, caused by Plasmodium spp. infections, is one of the most significant life-threatening infectious diseases to humans worldwide. There are many efforts and studies have been performed in order to develop effective vaccines, several potential vaccine candidates targeted against pre-erythrocytic, erythrocytic and sexual stages of Plasmodium falciparum are under various stages of clinical development [2, 3]. RTS, S/AS01 vaccine is a pre-erythrocytic stage vaccine based on the P. falciparum circumsporozoite protein (PfCSP) [4, 5]. It is not hard to see that pfcsp is a very important gene for the host immune response to the P. falciparum invasion
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