Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis.
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.
Tran
Mai H
MH
Helminth Biology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
Pearson
Mark S
MS
Bethony
Jeffrey M
JM
Smyth
Danielle J
DJ
Jones
Malcolm K
MK
Duke
Mary
M
Don
Tegan A
TA
McManus
Donald P
DP
Correa-Oliveira
Rodrigo
R
Loukas
Alex
A
D000818:Animals; D005243:Feces / Q000469:parasitology; D005260:Female; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology; D010270:Parasite Egg Count; D011994:Recombinant Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology* / Q000302:isolation & purification; D012555:Schistosomiasis mansoni / Q000276:immunology*; D059470:Tetraspanins
D015801:Helminth Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C512650:TSPAN2 protein, human; D059470:Tetraspanins