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

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      Abstract

      Background

      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.

      Methods

      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.

      Results

      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.

      Conclusions

      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.

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      Most cited references 46

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            Author and article information

            Affiliations
            [ ]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
            Contributors
            avallejo@inmuno.org
            nmartinez@inmuno.org
            alejatobongir@gmail.com
            jackelinealger@yahoo.es
            marcuslacerda@uol.com.br
            andrey.Kajava@crbm.cnrs.fr
            marevalo@inmuno.org
            sherrera@inmuno.org
            Journal
            Malar J
            Malar. J
            Malaria Journal
            BioMed Central (London )
            1475-2875
            12 April 2016
            12 April 2016
            2016
            : 15
            27067024
            4828788
            1263
            10.1186/s12936-016-1263-0
            © Vallejo et al. 2016

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), 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 ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

            Funding
            Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
            Award ID: U19AI089702
            Award ID: 1R01AI12123701
            Award Recipient :
            Categories
            Research
            Custom metadata
            © The Author(s) 2016

            Infectious disease & Microbiology

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