Document Type
Journal Article
Publication Date
3-2012
Journal
PLoS Neglected Tropical Diseases
Volume
Volume 6, Issue 3
Inclusive Pages
Article number e1564
Keywords
Antigens; Helminth--immunology; Schistosomiasis--prevention & control; Tetraspanins--immunology
Abstract
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 IgG1 and IgG3 from putatively resistant individuals resident in S. mansoniendemic 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
APA Citation
Pearson, M. S., Pickering, D. A., McSorley, H. J., Bethony, J. M., Tribolet, L., Dougall, A. M., Hotez, P.J., Loukas, A. (2012). Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen sm-TSP-2. PLoS Neglected Tropical Diseases, 6(3)
Peer Reviewed
1
Open Access
1
Included in
Medical Immunology Commons, Medical Microbiology Commons, Parasitic Diseases Commons, Parasitology Commons
Comments
Reproduced with permission of PLoS Neglected Tropical Diseases.