Schistosomes are extracellular blood flukes that can survive for many years within the human vascular system. Since the worms interact closely with their host, performing functions such as nutrient uptake and attachment that are normally performed by integral surface membrane proteins, the parasites must have developed mechanisms for avoiding immune attack directed at these proteins. Our goal is to determine whether these functional, host-exposed, schistosome membrane proteins can be effective targets of a schistosomiasis vaccine. If successful, this novel vaccination strategy should also be effective against other diseases caused by helminth parasites. Towards our goal, we have obtained several full-length Schistosoma mansoni cDNA clones, three of which encode surface membrane proteins that we have shown to be present at the host/parasite interface in living worms. These include a glucose transporter, an amino acid permease homologue and the surface antigen, SM23. All have been expressed to high levels within recombinant insect cells. In this application, we propose to focus our efforts on the three bona fide schistosome host-interactive membrane proteins (HIMPs) and perform the definitive studies that win ascertain whether HIMPs can be targets of an effective schistosomiasis vaccine. We will use both conformationally native, recombinant protein and naked DNA expression plasmids as immunogens to induce cellular and/or humoral immune responses against host-exposed epitopes on the HIMPs. Successfully immunized mice will be tested for their ability to resist schistosome infection. A library of recombinant antibodies (rAbs) will be generated from the spleens of successfully immunized mice and screened for clones that display surface epitope recognition. Purified rAbs from positive clones will be tested for their ability to passively transfer protection against cercariaI infection. Host-exposed epitopes will be determined and used to design improved vaccine candidates.
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