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

Tran, Mai H., Pearson, Mark S., Bethony, Jeffrey M., Smyth, Danielle J., Jones, Malcolm K., Duke, Mary, Don, Tegan A., McManus, Donald P., Correa-Oliveira, Rodrigo, and Loukas, Alex (2006) Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nature Medicine, 12 (7). pp. 835-840.

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Abstract

Schistosomes are blood-dwelling flukes that infect 200 million people worldwide and are responsible for hundreds of thousands of deaths annually. 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.

Item ID: 34130
Item Type: Article (Research - C1)
ISSN: 1546-170X
Funders: National Health and Medical Research Council of Australia (NHMRC), Wellcome Trust (WT), Australian Postgraduate Award (APA), Fogarty International Center, National Institutes of Health (FICNIH)
Projects and Grants: NHMRC R. Douglas Wright Career Development Award, FICNIH International Research Scientist Award
Date Deposited: 22 Sep 2016 05:12
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060599 Microbiology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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