Spleen cells of mice vaccinated with radiation-attenuated Schistosoma mansoni cercariae were used to produce monoclonal antibodies directed against newly transformed schistosomular surface antigens. One of these monoclonal antibodies recognized a polypeptide of 18 kDa. This glycoprotein was purified by monoclonal antibody immunoaffinity chromatography and a polyclonal antiserum was prepared against it. Immunofluorescence assays showed that the polyclonal antiserum bound to the surface of newly transformed schistosomula and lung-stage organisms but not to the surface of liver-stage and adult worms. Using this polyclonal antiserum we isolated recombinant clones from an adult worm cDNA expression library constructed in Xgtll. Clone 654.2 contained an insert of 0.52 kilobase and hybridized to a 1.2-kilobase mRNA species from adult worms. Most importantly, clone 654.2 produced a fusion protein of 125 kDa that was reactive with sera of vaccinated mice that are capable of transferring resistance. This result encourages future vaccination trials with the fusion protein.High levels of resistance to Schistosoma mansoni challenge infection can be induced in mice, rats, and baboons by vaccination with radiation-attenuated cercariae. At least in mice and rats, this resistance can be passively transferred to naive recipients using serum or purified immunoglobulins, indicating the importance of humoral immune responses in this resistance. The most consistent transfer of resistance is achieved when immune sera are administered while the schistosomula are in residence in the lungs. All such sera, including those of vaccinated mice, rats, and rabbits and of infected rats, contain antibodies that bind to the surface of lung-stage and newly transformed schistosomula. In contrast, sera from mice chronically infected with S. mansoni do not consistently transfer resistance, and antibodies in these sera do not bind to the surface of lung-stage schistosomula (reviewed in ref. 1). It is therefore likely that resistance following vaccination with radiation-attenuated cercariae is mediated by antibody binding to epitopes exposed on the surface of newly transformed and lung-stage schistosomula.Several S. mansoni proteins have recently been molecularly cloned and expressed in Escherichia coli; however, none of these appears to be localized on the surface of early developmental stages (2-5).Our approach to identifying potential immunoprophylactic antigens was to prepare monoclonal antibodies (mAb) from spleens of vaccinated mice and to screen such antibodies for their ability to immunoprecipitate surface-labeled schistosomular polypeptides. By this method we obtained a mAb, designated 654B2/1, that reacted with a single 18-kDa surface-labeled polypeptide. We purified this antigen and prepared a polyclonal antiserum (anti-654) against it. Immunofluorescence studies using anti-654 showed that some epitopes on the antigen are exposed not only on the surface of newly transformed schistosomula but also on the surface of lung-stage schistos...