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 乙肝表面抗原多肽疫苗。在这一框架内，有两个具体目标 被追捕。一是建立免疫的基本机制 对合成的病毒多肽的反应。这将通过使用 含有122-137个氨基酸序列的环状合成肽 其中主要多肽(P25)来源于HBs Ag/ayw。两种剂型 多肽--胶束结构中的聚集物，并与 破伤风类毒素或合成聚(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 将对迟发性超敏反应进行研究。这些数据应该有助于 为已接种疫苗的个人制定免疫时间表 单独接种破伤风类毒素和未接种过的婴儿 接种乙肝表面抗原破伤风类毒素。这样做的第二个目的是 这项研究是为了定义与乙肝表面抗原相关的单个表位。这 将通过合成一组不同的合成肽来完成，并通过 利用一组明确的抗-HBs单抗 具体细节。最后，与每一个相关的关键表位 将对合成碎片进行分析。这些研究将进行 具有环状和线状的多肽。与每一种氨基酸相关的氨基酸 将对表位进行多种氨基酸修饰进行分析 协议。每种单独的多肽制剂也将进行其测试 与自然感染的人抗-HBs结合的能力 个人。如果额外的关键抗原决定簇 成立后，有可能成立一个以上的公司 独特的合成乙肝表面抗原多肽将产生一种具有更强 潜在的免疫原性。最后，这些研究应该提供信息 另一种化学合成乙肝的疗效研究 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.