IMMUNE RESPONSE TO SYNTHETIC HBSAG PEPTIDES

拟议研究的总体目标是开发一种有效的合成物

The overall goal of the proposed study is to develop an effective synthetic HBsAg peptide vaccine. Within this framework two specific aims will be pursued. The first is to establish the basic mechanism of the immune response to a synthetic viral peptide. This will be carried out by using a cyclic synthetic peptide containing the amino acid sequence from 122 to 137 of the major polypeptide (P25) derived from HBsAg/ayw. Two formulations of peptide--aggregated material in micelle structure and conjugated to either tetanus toxoid or synthetic poly(DL-alanine)-poly(L-lysine) -- will be used to immunize BALB/c and nude mice. The interaction of T and B lymphocytes, the functions of T-suppressor, T-helper, and natural killer cells, and a delayed-type hypersensitivity will be studied. These data should aid in the formulation of an immunization schedule for individuals who have been preimmunized with tetanus toxoid alone and for infants who have not been inoculated with either tetanus toxoid of HBsAg. The second aim of this study is to define the individual epitopes associated with HBsAg. This will be done by synthesizing a panel of different synthetic peptides and by utilizing a panel of monoclonal anti-HBs antibodies with defined specificities. Finally, the critical epitope associated with each synthetic fragment will be analyzed. These studies will be carried out with cyclic and linear peptides. The amino acids associated with each epitope will be analyzed with a variety of amino acid modification protocols. Each individual peptide preparation will also be tested for its ability to bind human anti-HBs obtained from naturally infected individuals. If additional critical antigenic determinants are established, it is possible that the incorporation of more than one distinct synthetic HBsAg peptide would yield a vaccine with greater immunogenic potential. Finally, these studies should provide information on the efficacy of an alternative chemically synthesized hepatitis B vaccine.