IMMUNE RESPONSE TO SYNTHETIC HBSAG PEPTIDES

这项研究的总体目标是开发一种有效的合成药物， HBsAg肽疫苗。 在这一框架内，将有两个具体目标： 追求。 一是建立基本的免疫机制 对合成病毒肽的反应。 这将通过使用 含有122 - 137氨基酸序列的环状合成肽 主要多肽（P25）来源于HBsAg/ayw。 的两种制剂 肽-胶束结构中的聚集材料，并与 破伤风类毒素或合成的聚（DL-丙氨酸）-聚（L-赖氨酸）-将被使用 免疫BALB/c和裸鼠。 T和B淋巴细胞的相互作用， T抑制细胞、T辅助细胞和自然杀伤细胞的功能，以及 将研究迟发型超敏反应。 这些数据应该有助于 为已接种疫苗的个人制定免疫接种时间表， 仅用破伤风类毒素预先免疫的婴儿， 接种破伤风类毒素或HBsAg。 第二个目的是 研究的目的是确定与HBsAg相关的单个表位。 这 将通过合成一组不同的合成肽， 利用一组单克隆抗-HBs抗体， 特殊性 最后，与每一个相关的关键表位 将分析合成片段。 这些研究将在 环状和线性肽。 与每一种蛋白质相关的氨基酸 表位将用各种氨基酸修饰进行分析 协议. 还将测试每种单独的肽制剂的 结合从自然感染的人中获得的人抗-HBs的能力 个体 如果额外的关键抗原决定簇 成立，有可能是一个以上的合并 一种独特的合成HBsAg肽将产生一种疫苗， 免疫原性潜力。 最后，这些研究应提供信息， 一种替代化学合成的B型肝炎病毒的疗效 疫苗

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.