AVIRULENT SALMONELLA SP-10 VACCINE FOR SECRETORY IMMUNITY

用于分泌免疫的无毒沙门氏菌 SP-10 疫苗

• 批准号: 3735613
• 负责人: JOHN HERR
• 金额: --
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3735613
• 关键词: Macaca fascicularis; Salmonella vaccines; active immunization; affinity chromatography; antibody; antigens; cervix; contraceptives; drug design /synthesis /production; drug screening /evaluation; enzyme linked immunosorbent assay; female; fertility immunology; gut associated lymphoid tissue; immunoglobulins; in vitro fertilization; laboratory mouse; laboratory rabbit; mucus; oral contraceptives; ovary; plasma cells; radioimmunoassay; secretion; secretory immune system; sperm; stoichiometry; uterus; vaccines

The primary goal of this research proposal is to develop an oral contraceptive vaccine and to study the ability of this oral vaccine to induce infertility and secretory immunity within the female reproductive tract. The oral recombinant contraceptive vaccine to be developed will consist of avirulent strains of Salmonella which will be genetically engineered to express the human sperm immunogen SP-10. The avirulent strains of Salmonella will induce immunity by stimulating the gut associated lymphoid tissues [GALT] to dispel populations of specific antibody secreting cells which will populate the female reproductive organs. Experiments will be conducted on the cynomolgus monkey, Macca fascicularis. During the initial phase of the work the SP-10 immunogen will be engineered into avirulent strains of Salmonella and the stability and immunogenicity of the constructs evaluated in mice. In parallel with this goal, methods will be developed to measure specific antibody concentrations in the fluids and mucus of macaque ovarian follicles, oviducts, uterus and cervix and to determine the numbers and location of specific antibody secreting cells arising in these organs and in the circulation following parenteral immunization. Having developed methods of measuring immune responses in the monkey female tract, the effect of the oral contraceptive vaccine on secretory immunity within the ovaries, oviducts, uterus, cervix and circulation will be evaluated in monkeys. Most importantly, the anti-fertility potential of the oral contraceptive vaccine will be evaluated. Infertility will be correlated with levels of serum antibody as well as the degree to which secretory immunity was induced within the female tract. Finally, antibodies to SP-10 from serum and reproductive tract secretions will be studied for their ability to inhibit monkey in vitro fertilization. Using affinity purified antibodies, the precise stoichiometry of immunoglobulin required for inhibitory effects will be determined and these amounts compared to antibody levels induced within follicular, oviductal and cervical secretions by oral immunization. The sperm based recombinant oral contraceptive vaccine to be developed in this program will provide fundamental information on oviductal secretory immunity with wide application as a model for understanding contraceptive vaccine action.

这项研究提案的主要目标是开发一种口语 避孕疫苗和研究这种口服疫苗的能力 诱导雌性生殖不孕症和分泌性免疫 一条小路。即将开发的口服重组避孕疫苗将 由无毒的沙门氏菌菌株组成，这将是遗传上的 经改造后可表达人类精子免疫原SP-10。无毒的 沙门氏菌菌株通过刺激肠道诱导免疫力 相关淋巴组织[GALT]以驱散特定的 抗体分泌细胞，这些细胞将填充女性生殖 器官。实验将在食蟹猴Macca身上进行 束状肌。 在工作的初始阶段，将对SP-10免疫原进行工程改造 沙门氏菌弱毒株的稳定性和免疫原性 在小鼠身上评估的结构。与此目标并行的是，方法 将被开发用于测量体液中的特定抗体浓度 猕猴卵巢卵泡、输卵管、子宫和宫颈的粘液以及 确定特异性抗体分泌细胞的数量和位置 在这些器官和肠外循环中产生的 免疫接种。已经开发出测量免疫反应的方法 口服避孕疫苗对猴炎的影响 卵巢、输卵管、子宫、宫颈和 将对猴子的循环进行评估。 最重要的是，口服避孕药的抗生育潜力 将对疫苗进行评估。不孕症将与血液中的 血清抗体以及分泌性免疫的程度 在女性生殖道内诱导。最后，血清中的SP-10抗体 生殖道分泌物将被研究它们是否有能力 抑制猴体外受精。使用亲和纯化的抗体， 抑制作用所需的免疫球蛋白的精确化学计量 将被测定，并将这些数量与诱导的抗体水平进行比较 在卵泡、输卵管和宫颈分泌物内口服免疫。 以精子为基础的重组口服避孕疫苗将于#年开发 本节目将提供有关输卵管分泌的基本信息 免疫学作为了解避孕药具的一种模式有着广泛的应用 疫苗行动。