Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

Tapia, Chenet, Escalante, Durand Salomon, Lucas Carmen, Bacon

Description

A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin related anonymous protein (TRAP). Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity.

Sujets

• Malaria
• Plasmodium vivax

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English

Extrait

Chenetet al.Malaria Journal2012,11:68 http://www.malariajournal.com/content/11/1/68

R E S E A R C H

Open Access

Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax 1,2,3 1 2,3 1 1 Stella M Chenet , Lorena L Tapia , Ananias A Escalante , Salomon Durand , Carmen Lucas and 1,4* David J Bacon

Abstract Background:A major concern in malaria vaccine development is genetic polymorphisms typically observed amongPlasmodiumisolates in different geographical areas across the world. Highly polymorphic regions have been observed inPlasmodium falciparumandPlasmodium vivaxantigenic surface proteins such as Circumsporozoite protein (CSP), Duffybinding protein (DBP), Merozoite surface protein1 (MSP1), Apical membrane antigen1 (AMA1) and Thrombospondin related anonymous protein (TRAP). Methods:Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens inP. vivaxamong 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results:The structured diversity found inP. vivaxpopulations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of thetrap, dbpandama1genes. Conclusions:It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity. Keywords:Malaria,Plasmodium vivax, Vaccine candidates, Haplotypes

Background Malaria is one of the major global public health pro blems that affect most tropical regions of the world. Even thoughPlasmodium falciparumis the most viru lent, it is estimated thatPlasmodium vivaxproduces around 80 to 300 million clinical cases per year [1]. Furthermore, there have been several reports of severe P. vivaxmalaria cases in the last few years [24]. In 2008, 560,221 malaria cases were reported in the Ameri cas [5]; 74.2% of them caused byP. vivaxand 25.7% by P. falciparum[1]. About 90% of these malaria cases ori ginated in the Amazon basin shared by Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Venezuela,

* Correspondence: [e-mail] 1 Parasitology Program, Naval Medical Research Unit No. 6, Lima, Peru Full list of author information is available at the end of the article

Suriname and Peru [5], whereas the other 10% was con tributed by nonAmazon regions. Developing a vaccine forP. vivaxrepresents a major challenge especially considering the lack ofin vitrocul tures. Thus, current efforts focus on orthologs ofP. fal ciparum. Over the past four decades, experiments performed in animals and human subjects have led to the development of severalPlasmodiumvaccine candi dates. Antigenic surface proteins such as the Circum sporozoite protein (CSP), Thrombospondin related anonymous protein (TRAP), Duffybinding protein (DBP), Merozoite surface protein1 (MSP1) and Apical membrane antigen1 (AMA1) are currently being eval uated as vaccine candidates in clinical trials [1,68]. The CSP is one of the most extensively studied antigens and it is involved in the motility and invasion of the sporo zoite during its entrance in the hepatocyte [9].PvCSP

© 2012 Chenet et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.