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
- 66Citations
- 70Captures
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- Citations66
- Citation Indexes65
- 65
- CrossRef58
- Patent Family Citations1
- 1
- Captures70
- Readers70
- 70
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
10.1371/journal.pntd.0001564; 10.1371/journal.pntd.0001564.t001; 10.1371/journal.pntd.0001564.g003; 10.1371/journal.pntd.0001564.g001; 10.1371/journal.pntd.0001564.g005; 10.1371/journal.pntd.0001564.g002; 10.1371/journal.pntd.0001564.t002; 10.1371/journal.pntd.0001564.g004; 10.1371/journal.pntd.0001564.g006
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