CORE--ORAL RECOMBINANT SALMONELLA ANTIFERTILITY VACCINES CORE

最终目标是构建一个或多个安全、有效、 重组无毒沙门氏菌疫苗株，每株表达一株或 更多的精子或卵子特异性抗原，在口服免疫后， 诱导免疫反应以抑制和/或阻止受精 进程。一般来说，沙门氏菌的种类会因以下原因而减弱 引入Delta/CyA/Delta/CRP突变，并进一步修改以 降低血液中的存活率，在完全无毒的情况下排泄 非免疫原性形式，自然界存活率降低，概率最小 为那些未被选举接种疫苗的人提供免疫接种。遗传 精子特异性和卵特异性抗原的表达信息将 被包含在平衡致死型的多拷贝质粒载体上， 其中载体上的ASD+基因与Delta/ASD染色体互补 对二氨基甲酸(DAP)有需求的突变。遗传 确定重要的精子特异性和卵特异性抗原的信息 将基于中心其他成员进行的研究以及 由其他从事相关研究的科学家提出。带有DNA的载体 插入物的设计和构造将增强转录和 翻译和减少蛋白质产物的分解。我们还将 使用可用的最佳方法来增强和/或限制类型 通过包含编码佐剂的序列的免疫应答 增强SIgA粘膜的增强剂和/或调节剂和特异性表位 或免疫球蛋白体液或各种细胞免疫反应。各种不同的 构建将通过一系列体外测试和S。 鼠伤寒沙门氏菌和霍乱链球菌的稳定性和 对小鼠和兔的免疫原性。适宜伤寒和甲型副伤寒沙门氏菌 构造也将用于灵长类动物，并最终用于人类。 这项研究将利用现代技术在以下领域进行 微生物学、免疫学、遗传学、分子生物学和动物学。

The ultimate goal is to construct one or more safe, efficacious, recombinant avirulent Salmonella vaccine strains, each expressing one or more sperm- or egg-specific antigens that would, upon oral immunization, induce immune responses to inhibit and/or prevent the fertilization process. In general, species of Salmonella will be attenuated by introduction of delta/cya/delta/crp mutations, and further modified to decrease survivability in blood, to be excreted in a totally avirulent nonimmunogenic form with reduced survival in nature and minimal probability for causing immunization of those not elected to be immunized. Genetic information for expression of sperm-specific and egg-specific antigens will be contained on multi-copy plasmid vectors of the balanced lethal type, wherein the asd+ gene on the vector complements a delta/asd chromosomal mutation imposing a requirement for diaminopimelic acid (DAP). Genetic information defining important sperm-specific and egg-specific antigens will be based on studies being conducted by other Center members as well as by other scientists conducting related research. The vectors with DNA inserts will be designed and constructed to enhance transcription and translation and to reduce breakdown of the protein product. We will also employ the best available methods to enhance and/or restrict the type of immune response by inclusion of sequences encoding adjuvants, immune enhancers and/or modulators and specific epitopes to enhance SIgA mucosal or IgG humoral or various cellular immune responses. The various constructs will be evaluated in a diversity of in vitro tests and the S. typhimurium and S. choleraesuis derivatives for stability and immunogenicity in mice and rabbits. Suitable S. typhi and S. paratyphi A constructs will also be made for use with primates and ultimately humans. The research will make use of modern technologies in the fields of microbiology, immunology, genetics, molecular biology and animal sciences.