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: 3757362
• 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/3757362
• 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.

本研究计划的主要目标是发展一种口语