• Record: found
  • Abstract: found
  • Article: found
Is Open Access

Global genetic diversity of the Plasmodium vivax transmission-blocking vaccine candidate Pvs48/45

Read this article at

      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



      Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity, suggesting its potential as a P. vivax transmission-blocking vaccine candidate. To determine sequence polymorphism of natural parasite isolates and its potential influence on the protein structure, all pvs48/45 sequences reported in databases from around the world as well as those from low-transmission settings of Latin America were compared.


      Plasmodium vivax parasite isolates from malaria-endemic regions of Colombia, Brazil and Honduras (n = 60) were used to sequence the Pvs48/45 gene, and compared to those previously reported to GenBank and PlasmoDB (n = 222). Pvs48/45 gene haplotypes were analysed to determine the functional significance of genetic variation in protein structure and vaccine potential.


      Nine non-synonymous substitutions (E35K, Y196H, H211N, K250N, D335Y, E353Q, A376T, K390T, K418R) and three synonymous substitutions (I73, T149, C156) that define seven different haplotypes were found among the 282 isolates from nine countries when compared with the Sal I reference sequence. Nucleotide diversity (π) was 0.00173 for worldwide samples (range 0.00033–0.00216), resulting in relatively high diversity in Myanmar and Colombia, and low diversity in Mexico, Peru and South Korea. The two most frequent substitutions (E353Q: 41.9 %, K250N: 39.5 %) were predicted to be located in antigenic regions without affecting putative B cell epitopes or the tertiary protein structure.


      There is limited sequence polymorphism in pvs48/45 with noted geographical clustering among Asian and American isolates. The low genetic diversity of the protein does not influence the predicted antigenicity or protein structure and, therefore, supports its further development as transmission-blocking vaccine candidate.

      Related collections

      Most cited references 46

      • Record: found
      • Abstract: found
      • Article: not found

      MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.

      We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis (MEGA) software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis. In version 6.0, MEGA now enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface (GUI) to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from free of charge.
        • Record: found
        • Abstract: found
        • Article: not found

        CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.

        The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.
          • Record: found
          • Abstract: found
          • Article: not found

          DnaSP v5: a software for comprehensive analysis of DNA polymorphism data.

           P Librado,  J Rozas (2009)
          DnaSP is a software package for a comprehensive analysis of DNA polymorphism data. Version 5 implements a number of new features and analytical methods allowing extensive DNA polymorphism analyses on large datasets. Among other features, the newly implemented methods allow for: (i) analyses on multiple data files; (ii) haplotype phasing; (iii) analyses on insertion/deletion polymorphism data; (iv) visualizing sliding window results integrated with available genome annotations in the UCSC browser. Freely available to academic users from: (

            Author and article information

            [ ]Malaria Vaccine and Drug Development Center, Cali, Colombia
            [ ]Facultad de Ciencias Médicas, Hospital Escuela Universitario, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras
            [ ]Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
            [ ]Centre de Recherches Biochimie Macromoléculaire (CRBM), Institut de Biologie Computationnelle (IBC), CNRS, University of Montpellier, Montpellier, France
            [ ]Institute of Bioengineering, University ITMO, Saint Petersburg, Russia
            [ ]Caucaseco Scientific Research Center, Cali, Colombia
            [ ]School of Health, Universidad del Valle, Cali, Colombia
            Malar J
            Malar. J
            Malaria Journal
            BioMed Central (London )
            12 April 2016
            12 April 2016
            : 15
            © Vallejo et al. 2016

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

            Funded by: FundRef, National Institute of Allergy and Infectious Diseases;
            Award ID: U19AI089702
            Award ID: 1R01AI12123701
            Award Recipient :
            Custom metadata
            © The Author(s) 2016

            Infectious disease & Microbiology


            Comment on this article