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Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2

PLoS Neglected Tropical Diseases, ISSN: 1935-2727, Vol: 6, Issue: 3, Page: e1564
2012
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Article Description

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG and IgG from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic. © 2012 Pearson et al.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84859197342&origin=inward; http://dx.doi.org/10.1371/journal.pntd.0001564; http://www.ncbi.nlm.nih.gov/pubmed/22428079; https://dx.plos.org/10.1371/journal.pntd.0001564.t001; http://dx.doi.org/10.1371/journal.pntd.0001564.t001; https://dx.plos.org/10.1371/journal.pntd.0001564.g003; http://dx.doi.org/10.1371/journal.pntd.0001564.g003; https://dx.plos.org/10.1371/journal.pntd.0001564.g001; http://dx.doi.org/10.1371/journal.pntd.0001564.g001; https://dx.plos.org/10.1371/journal.pntd.0001564.g005; http://dx.doi.org/10.1371/journal.pntd.0001564.g005; https://dx.plos.org/10.1371/journal.pntd.0001564.g002; http://dx.doi.org/10.1371/journal.pntd.0001564.g002; https://dx.plos.org/10.1371/journal.pntd.0001564.t002; http://dx.doi.org/10.1371/journal.pntd.0001564.t002; https://dx.plos.org/10.1371/journal.pntd.0001564.g004; http://dx.doi.org/10.1371/journal.pntd.0001564.g004; https://dx.plos.org/10.1371/journal.pntd.0001564; https://dx.plos.org/10.1371/journal.pntd.0001564.g006; http://dx.doi.org/10.1371/journal.pntd.0001564.g006; https://dx.doi.org/10.1371/journal.pntd.0001564.t002; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.t002; https://dx.doi.org/10.1371/journal.pntd.0001564; https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001564; https://dx.doi.org/10.1371/journal.pntd.0001564.g003; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g003; https://dx.doi.org/10.1371/journal.pntd.0001564.g001; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g001; https://dx.doi.org/10.1371/journal.pntd.0001564.t001; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.t001; https://dx.doi.org/10.1371/journal.pntd.0001564.g004; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g004; https://dx.doi.org/10.1371/journal.pntd.0001564.g006; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g006; https://dx.doi.org/10.1371/journal.pntd.0001564.g005; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g005; https://dx.doi.org/10.1371/journal.pntd.0001564.g002; https://journals.plos.org/plosntds/article/figure?id=10.1371/journal.pntd.0001564.g002; http://dx.plos.org/10.1371/journal.pntd.0001564.g006; http://dx.plos.org/10.1371/journal.pntd.0001564.g003; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pntd.0001564; http://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001564&type=printable; http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001564; https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0001564&type=printable; http://dx.plos.org/10.1371/journal.pntd.0001564.g004; http://dx.plos.org/10.1371/journal.pntd.0001564.g002; http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0001564; http://dx.plos.org/10.1371/journal.pntd.0001564.t001; http://dx.plos.org/10.1371/journal.pntd.0001564.g001; http://dx.plos.org/10.1371/journal.pntd.0001564.t002; http://dx.plos.org/10.1371/journal.pntd.0001564; http://dx.plos.org/10.1371/journal.pntd.0001564.g005

Mark S. Pearson; Darren A. Pickering; Henry J. McSorley; Jeffrey M. Bethony; Leon Tribolet; Annette M. Dougall; Peter J. Hotez; Alex Loukas; Kenji Hirayama

Public Library of Science (PLoS)

Medicine

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