scholarly journals Genetic Polymorphism and Natural Selection of Apical Membrane Antigen-1 in Plasmodium falciparum Isolates from Vietnam

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1903
Author(s):  
Jung-Mi Kang ◽  
Hương Giang Lê ◽  
Tuấn Cường Võ ◽  
Haung Naw ◽  
Won Gi Yoo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Amino Acid ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Geographical Regions ◽  
Major Amino Acid ◽  
Selection Of

Apical membrane antigen-1 of Plasmodium falciparum (PfAMA-1) is a leading malaria vaccine candidate antigen. However, the genetic diversity of pfama-1 and associated antigenic variation in global P. falciparum field isolates are major hurdles to the design of an efficacious vaccine formulated with this antigen. Here, we analyzed the genetic structure and the natural selection of pfama-1 in the P. falciparum population of Vietnam. A total of 37 distinct haplotypes were found in 131 P. falciparum Vietnamese isolates. Most amino acid changes detected in Vietnamese pfama-1 were localized in the ectodomain, domains I, II, and III. Overall patterns of major amino acid changes in Vietnamese pfama-1 were similar to those of global pfama-1, but the frequencies of the amino acid changes slightly differed by country. Novel amino acid changes were also identified in Vietnamese pfama-1. Vietnamese pfama-1 revealed relatively lower genetic diversity than currently analyzed pfama-1 in other geographical regions, and suggested a distinct genetic differentiation pattern. Evidence for natural selection was detected in Vietnamese pfama-1, but it showed purifying selection unlike the global pfama-1 analyzed so far. Recombination events were also found in Vietnamese pfama-1. Major amino acid changes that were commonly identified in global pfama-1 were mainly localized to predicted B-cell epitopes, RBC-binding sites, and IUR regions. These results provide important information for understanding the genetic nature of the Vietnamese pfama-1 population, and have significant implications for the design of a vaccine based on PfAMA-1.

scholarly journals A Diversity-Covering Approach to Immunization with Plasmodium falciparum Apical Membrane Antigen 1 Induces Broader Allelic Recognition and Growth Inhibition Responses in Rabbits

2008 ◽  
Vol 76 (6) ◽  
pp. 2660-2670 ◽  
Author(s):  
Edmond J. Remarque ◽  
Bart W. Faber ◽  
Clemens H. M. Kocken ◽  
Alan W. Thomas
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Growth Inhibition ◽  
Apical Membrane ◽  
Recombinant Expression ◽  
Methylotrophic Yeast ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen ◽  
Amino Acid Variability

ABSTRACT Plasmodium falciparum apical membrane antigen 1 (PfAMA1), a candidate malaria vaccine, is polymorphic. This polymorphism is believed to be generated predominantly under immune selection pressure and, as a result, may compromise attempts at vaccination. Alignment of 355 PfAMA1 sequences shows that around 10% of the 622 amino acid residues can vary between alleles and that linkages between polymorphic residues occur. Using this analysis, we have designed three diversity-covering (DiCo) PfAMA1 sequences that take account of these linkages and, when taken together, on average incorporate 97% of amino acid variability observed. For each of the three DiCo sequences, a synthetic gene was constructed and used to transform the methylotrophic yeast Pichia pastoris, allowing recombinant expression. All three DiCo proteins were reactive with the reduction-sensitive monoclonal antibody 4G2, suggesting the DiCo sequences had conformations similar to those of naturally occurring PfAMA1. Rabbits were immunized with FVO strain PfAMA1 or with the DiCo proteins either individually or as a mixture. Antibody titers and the ability to inhibit parasite growth in vitro were determined. Animals immunized with the DiCo mix performed similarly to animals immunized with FVO AMA1 when measured against FCR3 strain parasites but outperformed animals immunized with FVO AMA1 when assessed against other strains. The levels of growth inhibition (∼70%) induced by the mix of three DiCo proteins were comparable for FVO, 3D7, and HB3, suggesting that a considerable degree of diversity in AMA1 is adequately covered. This suggests that vaccines based upon the DiCo mix approach provide a broader functional immunity than immunization with a single allele.

scholarly journals Genetic diversity and effect of natural selection at apical membrane antigen-1 (AMA-1) among Iranian Plasmodium vivax isolates

2014 ◽  
Vol 61 (5) ◽  
pp. 385-393 ◽  
Author(s):  
Ahmad Reza Esmaeili Rastaghi ◽  
Fatemeh Nedaei ◽  
Hossein Nahrevanian ◽  
Nazanin Hoseinkhan
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Plasmodium Vivax ◽  
Apical Membrane ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

scholarly journals Natural selection and genetic diversity of domain I of Plasmodium falciparum apical membrane antigen-1 on Bioko Island

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ya-Nan Wang ◽  
Min Lin ◽  
Xue-Yan Liang ◽  
Jiang-Tao Chen ◽  
Dong-De Xie ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Amino Acid ◽  
Malaria Vaccine ◽  
Apical Membrane ◽  
Three Dimensional ◽  
B Cell Epitopes ◽  
Apical Membrane Antigen 1 ◽  
Bioko Island ◽  
Domain I

Abstract Background Plasmodium 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. Methods 214 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. Results 131 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. Conclusions Patterns 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.

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