Abstract
BackgroundPlasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. However, antigenic variation and diversity of PfAMA-1 are still major problems to design a universal malaria vaccine based on this antigen, especially against domain I (DI). Detail understanding of the PfAMA-1 gene polymorphism can provide useful information on this potential vaccine component. Here, general characteristics of genetic structure and the effect of natural selection of DIs among Bioko P. falciparum isolates were analysed.Methods214 blood samples were collected from Bioko Island patients with P. falciparum malaria between 2011 and 2017. A fragment spanning DI of PfAMA-1 was amplified by nested polymerase chain reaction and sequenced. Polymorphic characteristics and the effect of natural selection were analysed using MEGA 5.0, DnaSP 6.0 and Popart programs. Genetic diversity in 576 global PfAMA-1 DIs were also analysed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 program.Results131 different haplotypes of PfAMA-1 were identified in 214 Bioko Island P. falciparum isolates. Most amino acid changes identified on Bioko Island were found in C1L. 32 amino acid changes identified in PfAMA-1 sequences from Bioko Island were found in predicted RBC-binding sites, B cell epitopes or IUR regions. Overall patterns of amino acid changes of Bioko PfAMA-1 DIs were similar to those in global PfAMA-1 isolates. Differential amino acid substitution frequencies were observed for samples from different geographical regions. Eight new amino acid changes of Bioko island isolates were also identified and their three-dimensional protein structural consequences were predicted. Evidence for natural selection and recombination event were observed in global isolates.ConclusionsPatterns of nucleotide diversity and amino acid polymorphisms of Bioko Island isolates were similar to those of global PfAMA-1 DIs. Balancing natural selection across DIs might play a major role in generating genetic diversity in global isolates. Most amino acid changes in DIs occurred in predicted B-cell epitopes. Novel sites mapped on a three dimensional structure of PfAMA-1 showed that these regions were located at the corner. These results may provide significant value in the design of a malaria vaccine based on this antigen.
Highlights
Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine
Most amino acid changes were in C1 region (14 amino acid changes), and these amino acid changes were distributed throughout each Bioko PfAMA-1 haplotype
The overall pattern of nucleotide diversity and distribution of amino acid changes of PfAMA-1 on Bioko Island is similar to those from other global isolates, several novel amino acid changes are found on Bioko Island
Summary
Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. Fifteen countries accounted for 80% of global malaria deaths in 2017, and the 10 highest burdened African countries saw an estimated 3.5 million more malaria cases in 2017 compared with the previous year [2]. In 2004, the government and private parties formed a Public–Private Partnership that has spent the last 15 years controlling malaria on Bioko Island and parts of the mainland in an effort to reduce malaria’s burden on the population. The Bioko Island Malaria Control Project (BIMCP) implemented by the U.S NGO, Medical Care Development International (MCDI) and the Ministry of Health and Social Welfare of the Government of Equatorial Guinea, has reduced malaria prevalence from 74% (by thick blood smear) in 2003 to 11% (by rapid diagnostic test) in 2017 in children 2 to 14 years of age. It is still a major obstacle to public health and economic growth for countries in the tropics and subtropical regions [4]
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