Abstract
Backgroud RTS, S/AS01 is a Plasmodium falciparum circumsporozoite protein ( PfCSP ) based anti-malaria vaccine, but various genetic polymorphisms of PfCSP among global P. falciparum population could lead to mismatch against the PfCSP - based vaccine and reduce vaccine efficacy. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko as well as 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 analyzed 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 vaccine strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal. The overall vaccine efficacy might be influenced by the low proportion of vaccine-matched isolates in global parasites population. Genetic polymorphism and geographical characteristics should be considered for future improvement of RTS, S/AS01.
Assessing Malaria Vaccine Efficacy
