scholarly journals Genetic Diversity of Plasmodium vivax Reticulocyte Binding Protein 2b in Global Parasite Populations

2021 ◽  
Author(s):  
xuexing zhang ◽  
Haichao Wei ◽  
Yangminghui Zhang ◽  
Yan Zhao ◽  
Lin Wang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Binding Protein ◽  
Critical Role ◽  
Binding Region ◽  
Geographical Separation ◽  
Antibody Titers ◽  
Parasite Populations

Abstract BackgroundPlasmodium vivax reticulocyte binding protein 2b (PvRBP2b) plays a critical role in parasite invasion of reticulocytes by binding the transferring receptor 1. PvRBP2b is a vaccine candidate since the antibody titers against PvRBP2b recombinant proteins are negatively correlated with the parasitemia and risk of vivax malaria. This study aims to analyze the genetic diversity of the PvRBP2b gene in the global P. vivax populations. MethodsThe near full-length PvRBP2b nucleotide sequences (190-8349 bp) were obtained from 88 P. vivax isolates collected from the China–Myanmar border (n=44) and Thailand (n=44). Additional 224 sequences of PvRBP2b were retrieved from genome sequences from the global parasite populations. The genetic diversity, neutral selections, haplotypes distribution and genetic differentiation of PvRBP2b were examined. ResultsThe genetic diversity of PvRBP2b was distributed unevenly with the peak in the reticulocyte binding region in the N-terminus and subjected to the balancing selection. Several amino acid variants were found in all or nearly all endemic fields. However, the critical residues responsible for reticulocyte binding were highly conserved. There was substantial population differentiation according to the geographical separation. The distribution of haplotypes in the reticulocyte binding region varied among regions; even the two major haplotypes Hap_6 and Hap_8 were found in only five populations. ConclusionsOur data showed considerable genetic variations of PvRBPb in global parasite populations, and the geographic divergence may pose a challenge to PvRBP2b-based vaccine development.

scholarly journals Genetic diversity in two leading Plasmodium vivax malaria vaccine candidates AMA1 and MSP119 at three sites in India

2021 ◽  
Vol 15 (8) ◽  
pp. e0009652
Author(s):  
Sonal Kale ◽  
Veena Pande ◽  
Om P. Singh ◽  
Jane M. Carlton ◽  
Prashant K. Mallick
Keyword(s):  
Genetic Diversity ◽  
North America ◽  
South America ◽  
Plasmodium Vivax ◽  
Nucleotide Diversity ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Global Scale ◽  
High Genetic Diversity ◽  
Global Population

Plasmodium vivax, a major contributor to the malaria burden in India, has the broadest geographic distribution and shows higher genetic diversity than P. falciparum. Here, we investigated the genetic diversity of two leading P. vivax vaccine candidate antigens, at three geographically diverse malaria-endemic regions in India. Pvama1 and Pvmsp119 partial coding sequences were generated from one hundred P. vivax isolates in India (Chennai n = 28, Nadiad n = 50 and Rourkela n = 22) and ~1100 published sequences from Asia, South America, North America, and Oceania regions included. These data were used to assess the genetic diversity and potential for vaccine candidacy of both antigens on a global scale. A total of 44 single nucleotide polymorphism (SNPs) were identified among 100 Indian Pvama1 sequences, including 10 synonymous and 34 nonsynonymous mutations. Nucleotide diversity was higher in Rourkela and Nadiad as compared to Chennai. Nucleotide diversity measures showed a strong balancing selection in Indian and global population for domain I of Pvama1, which suggests that it is a dominant target of the protective immune response. In contrast, the Pvmsp119 region showed highly conserved sequences in India and across the Oceania, South America, North America and Asia, demonstrating low genetic diversity in the global population when compared to Pvama1. Results suggest the possibility of including Pvmsp119 in a multivalent vaccine formulation against P. vivax infections. However, the high genetic diversity seen in Pvama1 would be more challenging for vaccine development.

scholarly journals Genetic Diversity in New Members of the Reticulocyte Binding Protein Family in Thai Plasmodium vivax Isolates

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32105 ◽  
Author(s):  
Varakorn Kosaisavee ◽  
Usa Lek-Uthai ◽  
Rossarin Suwanarusk ◽  
Anne Charlotte Grüner ◽  
Bruce Russell ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Protein Family ◽  
New Members

scholarly journals Correction: Genetic Diversity in New Members of the Reticulocyte Binding Protein Family in Thai Plasmodium vivax Isolates

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
Author(s):  
Varakorn Kosaisavee ◽  
Usa Lek-Uthai ◽  
Rossarin Suwanarusk ◽  
Anne Charlotte Grüner ◽  
Bruce Russell ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Protein Family ◽  
New Members

scholarly journals Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates

2021 ◽  
Vol 17 (7) ◽  
pp. e1008864
Author(s):  
Duncan N. Ndegwa ◽  
Prasun Kundu ◽  
Jessica B. Hostetler ◽  
Alejandro Marin-Menendez ◽  
Theo Sanderson ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Culture System ◽  
Vaccine Development ◽  
Expression System ◽  
Critical Role ◽  
Blood Stage ◽  
Effective Vaccine ◽  
Mammalian Expression ◽  
Close Phylogenetic Relationship

Plasmodium vivax is responsible for the majority of malaria cases outside Africa. Unlike P. falciparum, the P. vivax life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against P. vivax blood stages would limit symptoms and pathology from such recurrent infections, and therefore could play a critical role in the control of this species. Vaccine development in P. vivax, however, lags considerably behind P. falciparum, which has many identified targets with several having transitioned to Phase II testing. By contrast only one P. vivax blood-stage vaccine candidate based on the Duffy Binding Protein (PvDBP), has reached Phase Ia, in large part because the lack of a continuous in vitro culture system for P. vivax limits systematic screening of new candidates. We used the close phylogenetic relationship between P. vivax and P. knowlesi, for which an in vitro culture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritise P. vivax blood-stage targets. A panel of P. vivax proteins predicted to function in erythrocyte invasion were expressed as full-length recombinant ectodomains in a mammalian expression system. Eight of these antigens were used to generate polyclonal antibodies, which were screened for their ability to recognize orthologous proteins in P. knowlesi. These antibodies were then tested for inhibition of growth and invasion of both wild type P. knowlesi and chimeric P. knowlesi lines modified using CRISPR/Cas9 to exchange P. knowlesi genes with their P. vivax orthologues. Candidates that induced antibodies that inhibited invasion to a similar level as PvDBP were identified, confirming the utility of P. knowlesi as a model for P. vivax vaccine development and prioritizing antigens for further follow up.

scholarly journals Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity

2020 ◽  
Vol 14 (7) ◽  
pp. e0008202 ◽  
Author(s):  
Jin-Hee Han ◽  
Jee-Sun Cho ◽  
Jessica J. Y. Ong ◽  
Ji-Hoon Park ◽  
Myat Htut Nyunt ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Neutral Selection ◽  
Erythrocyte Binding

scholarly journals Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yubing Hu ◽  
Lin Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
Myat Thu Soe ◽  
Chunyun Yu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Duffy Binding Protein ◽  
High Genetic Diversity ◽  
Low Level ◽  
Malaria Epidemiology ◽  
Greater Mekong Subregion

Abstract Background Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. Methods pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. Results The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. Conclusions The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.

Genetic diversity and natural selection of Duffy binding protein of Plasmodium vivax Korean isolates

Acta Tropica ◽  
2013 ◽  
Vol 125 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Hye-Lim Ju ◽  
Jung-Mi Kang ◽  
Sung-Ung Moon ◽  
Young-Yil Bahk ◽  
Pyo-Yun Cho ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Duffy Binding Protein ◽  
Selection Of

scholarly journals Use of a Plasmodium vivax genetic barcode for genomic surveillance and parasite tracking in Sri Lanka

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Rajika L. Dewasurendra ◽  
Mary Lynn Baniecki ◽  
Stephen Schaffner ◽  
Yamuna Siriwardena ◽  
Jade Moon ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Sri Lanka ◽  
Plasmodium Vivax ◽  
In Silico ◽  
In Silico Analysis ◽  
Minor Allele ◽  
Allele Frequencies ◽  
Single Nucleotide ◽  
Parasite Populations ◽  
Silico Analysis

Abstract Background Sri Lanka was certified as a malaria-free nation in 2016; however, imported malaria cases continue to be reported. Evidence-based information on the genetic structure/diversity of the parasite populations is useful to understand the population history, assess the trends in transmission patterns, as well as to predict threatening phenotypes that may be introduced and spread in parasite populations disrupting elimination programmes. This study used a previously developed Plasmodium vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics of P. vivax parasite isolates from Sri Lanka and to assess the ability of the SNP barcode for tracking the parasites to its origin. Methods A total of 51 P. vivax samples collected during 2005–2011, mainly from three provinces of the country, were genotyped for 40 previously identified P. vivax SNPs using a high-resolution melting (HRM), single-nucleotide barcode method. Minor allele frequencies, linkage disequilibrium, pair-wise FST values, and complexity of infection (COI) were evaluated to determine the genetic diversity. Structure analysis was carried out using STRUCTURE software (Version 2.3.4) and SNP barcode was used to identify the genetic diversity of the local parasite populations collected from different years. Principal component analysis (PCA) was used to determine the clustering according to global geographic regions. Results The proportion of multi-clone infections was significantly higher in isolates collected during an infection outbreak in year 2007. The minor allele frequencies of the SNPs changed dramatically from year to year. Significant linkage was observed in sample sub-sets from years 2005 and 2007. The majority of the isolates from 2007 consisted of at least two genetically distinct parasite strains. The overall percentage of multi-clone infections for the entire parasite sample was 39.21%. Analysis using STRUCTURE software (Version 2.3.4) revealed the high genetic diversity of the sample sub-set from year 2007. In-silico analysis of these data with those available from other global geographical regions using PCA showed distinct clustering of parasite isolates according to geography, demonstrating the usefulness of the barcode in determining an isolate to be indigenous. Conclusions Plasmodium vivax parasite isolates collected during a disease outbreak in year 2007 were more genetically diverse compared to those collected from other years. In-silico analysis using the 40 SNP barcode is a useful tool to track the origin of an isolate of uncertain origin, especially to differentiate indigenous from imported cases. However, an extended barcode with more SNPs may be needed to distinguish highly clonal populations within the country.

Sign in / Sign up

Export Citation Format

Share Document