SYNTHETIC PEPTIDE VACCINES FOR DENTAL CARIES

治疗龋齿的合成肽疫苗

基本信息

批准号：
3219134
负责人：
MARTIN A TAUBMAN
金额：
$ 33.69万
依托单位：
ADA FORSYTH INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-07-01 至 1996-04-30
项目状态：
已结题

项目摘要

Synthetic vaccines have been used to confer immunity on humans and also to orally elicit secretory antibody and mucosal protection. The overall aim of this proposed series of experiments will be to develop a synthetic vaccine which will be effective in protecting against dental caries. We will investigate enzymatic fragmentation of S. sobrinus and S. mutans GTFs in order to identify the epitopes on intact GTF to which human salivary antibody reacts. We will prepare human IgA and IgG antibody pools to S. sobrinus GTF and enzymatically digest GTF species and investigate epitopes associated with glucan-binding sites and with a catalytic site. We have outlined the structures of synthetic peptides which contain functionally relevant and structurally conserved regions of the glucosyltransferase enzymes derived from S. sobrinus and S. mutans. Theoretically, antibody directed to these structures will have enhanced potential to interfere with enzyme function and thereby inhibit dental caries. Particularly promising is the peptide containing a catalytic site of GTF. We will determine whether epitopes present on synthetic peptides react with (antigenicity), or elicit(immunogenicity) antibody that inhibits a function of the intact enzyme. The presence of functional activity of these peptides will be verified and compared to fragments from the parent molecules. Each peptide will be analyzed for antigenicity with human salivary IgA and serum antibody to GTFs. The ability of these peptides to generate protective immunity in an experimental dental caries model using both local and oral antigen administration will be investigated. We will also investigate the effects of synthetic peptide immunization on infection and disease caused by species of mutans streptococci other than species from which the peptide was derived. The most effective protective component(s) will be incorporated into a composite vaccine which will also be tested for protection in this system. The composite vaccine will incorporate all the protection-eliciting features of the GTF moieties and also the B and T cell epitopes required to initiate and sustain an immune response without any potentially harmful components. We will utilize both hybrid and MAP technologies to produce these composite vaccines. This proposal holds promise for further understanding of the relationship of GTF to dental caries and, most importantly, for the development of a dental caries vaccine for use in humans which is safe and elicits long-lasting protective immune response.

合成疫苗已被用于赋予人类免疫力，也用于口服引起分泌抗体和粘膜保护。总体目标这一系列实验的目的是开发一种合成的疫苗可有效预防龋齿。我们将研究 S. sobrinus 和 S. mutans GTF 的酶促断裂为了鉴定完整 GTF 上人类唾液所结合的表位抗体发生反应。我们将制备针对金黄色葡萄球菌的人 IgA 和 IgG 抗体库。 sobrinus GTF 和酶消化 GTF 物种并研究表位与葡聚糖结合位点和催化位点相关。我们有概述了合成肽的结构，其中包含功能葡萄糖基转移酶的相关和结构保守区域源自 S. sobrinus 和 S. mutans 的酶。理论上，抗体针对这些结构将具有更大的干扰潜力酶的功能，从而抑制龋齿。特别有前途是含有 GTF 催化位点的肽。我们将确定合成肽上存在的表位是否与（抗原性）反应，或引发（免疫原性）抗体，抑制完整的功能酶。这些肽的功能活性的存在将是验证并与母体分子的片段进行比较。各肽将与人唾液 IgA 和血清进行抗原性分析 GTF 抗体。这些肽产生保护作用的能力使用局部和口腔的实验性龋齿模型中的免疫将研究抗原施用。我们还将调查合成肽免疫对感染和疾病的影响按变形链球菌种类，而不是肽来源的种类被导出。最有效的保护成分是纳入复合疫苗中，该疫苗也将进行测试在此系统中进行保护。复合疫苗将包含所有 GTF 部分以及 B 和 T 细胞的保护诱导特征启动和维持免疫反应所需的表位，无需任何潜在有害成分。我们将同时使用混合和 MAP 生产这些复合疫苗的技术。该提案成立承诺进一步了解 GTF 与牙科的关系龋齿，最重要的是，对于龋齿的发展用于人类的疫苗，安全且能产生持久的保护作用免疫反应。