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Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis

Nature Medicine volume 12, pages 835–840 (2006)Cite this article

Abstract

Schistosomes are blood-dwelling flukes that infect 200 million people worldwide and are responsible for hundreds of thousands of deaths annually1. Using a signal sequence trap, we cloned from Schistosoma mansoni two cDNAs, Sm-tsp-1 and Sm-tsp-2, encoding the tetraspanin (TSP) integral membrane proteins TSP-1 and TSP-2. We raised antibodies to recombinant TSP fusion proteins and showed that both proteins are exposed on the surface of S. mansoni. Recombinant TSP-2, but not TSP-1, is strongly recognized by IgG1 and IgG3 (but not IgE) from naturally resistant individuals but is not recognized by IgG from chronically infected or unexposed individuals. Vaccination of mice with the recombinant proteins followed by challenge infection with S. mansoni resulted in reductions of 57% and 64% (TSP-2) and 34% and 52% (TSP-1) for mean adult worm burdens and liver egg burdens, respectively, over two independent trials. Fecal egg counts were reduced by 65–69% in both test groups. TSP-2 in particular provided protection in excess of the 40% benchmark set by the World Health Organization for progression of schistosome vaccine antigens into clinical trials. When coupled with its selective recognition by naturally resistant people, TSP-2 seems to be an effective vaccine antigen against S. mansoni.

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Figure 1: TSP-1 and TSP-2 are expressed in the outer tegument of adult S. mansoni.
Figure 2: Individuals who are putatively resistant to S. mansoni selectively recognize TSP-2, but chronically infected individuals do not.

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Acknowledgements

We thank M. Smout for assistance with figure preparations, W. Schroeder for technical assistance and D. Diemert and P. Hotez for comments on the manuscript and discussions. This work was supported by grants from the National Health and Medical Research Council of Australia (NHMRC) and The Wellcome Trust. A.L. is the recipi of an R. Douglas Wright Career Development Award from NHMRC. M.S.P. was supported by an Australian Postgraduate Award. J.M.B. is supported by an International Research Scientist Award from Fogarty International Center, US National Institutes of Health.

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Author notes

  1. Mai H Tran, Mark S Pearson and Jeffrey M Bethony: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Infectious Diseases and Immunology, Helminth Biology Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, 4006, Queensland, Australia

    Mai H Tran, Mark S Pearson, Danielle J Smyth, Malcolm K Jones, Mary Duke, Tegan A Don, Donald P McManus & Alex Loukas

  2. Department of Microbiology, Tropical Medicine and Immunology, George Washington University, 2300 I Street NW, Washington, 20037, DC, USA

    Jeffrey M Bethony

  3. Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil

    Jeffrey M Bethony & Rodrigo Correa-Oliveira

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Supplementary information

Supplementary Table 1

Identification of cohorts of Chronically Infected (CI) and Putatively Resistant (PR) individuals in the S. mansoni endemic area of Siquiera (n = 162). (PDF 59 kb)

Supplementary Table 2

Inclusion and exclusion rules for the assembly and maintenance of resistant cohorts. (PDF 69 kb)

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Tran, M., Pearson, M., Bethony, J. et al. Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nat Med 12, 835–840 (2006). https://doi.org/10.1038/nm1430

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