A mimotope peptide-based vaccine against Schistosoma mansoni: synthesis and characterization.
A panel of four mimotopes of the epitope recognized by the highly protective monoclonal antibody against Schistosoma mansoni (152-66-9B) was obtained by screening a solid-phase 8mer random peptide library. Three of the four mimotopes (p28, p29 and p30) were efficiently recognized in an in vitro radioimmunoassay by the monoclonal antibody and by sera from infected mice and one (p30) induced in vitro proliferation of primed lymphocytes. When the mimotopes were conjugated to bovine serum albumin (BSA) and the conjugates used to immunize C57BL/6J mice, only the p30-BSA-induced antibodies which were effective at complement-mediated killing of schistosomula. The level of complement-mediated killing obtained with the anti-p30 antibodies was comparable to that seen with serum from mice immunized with the protective 9B-antigen. Furthermore, following challenge infection of mimotope-BSA-immunized mice, a greater than 40% reduction in worm burden was observed in p30-BSA-immunized mice, a level comparable to that seen following immunization with the intact 9B-antigen. These results show that a simple synthetic peptide immunogen comprising an eight-amino acid mimotope of a conformational epitope on the 9B-antigen can induce protective immune responses against S. mansoni that are comparable to those obtained following immunization with the far more complex intact antigen. This mimotope may well represent a potential component of a synthetic peptide vaccine against S. mansoni. The inclusion of other B-cell- and T-cell-stimulating synthetic epitopes in such a vaccine, together with a more appropriate carrier, adjuvant and delivery systems may well result in a level of protection even greater than that seen with the single mimotope.
Arnon
R
R
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Tarrab-Hazdai
R
R
Steward
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D019151:Peptide Library; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D019151:Peptide Library; D014614:Vaccines, Synthetic; D003165:Complement System Proteins