Project Three: Assessing effects of anti-CD52g Mabs on STD pathogens in semen

项目三：评估抗 CD52g Mab 对精液中 STD 病原体的影响

• 批准号: 9977700
• 负责人: Deborah J Anderson
• 金额: $ 41.25万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-13 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977700
• 关键词: Aftercare; Antibodies; Antigens; Binding; Birth; Cell membrane; Cells; Cervix Mucus; Collaborations; Contraceptive Agents; Contraceptive methods; Developing Countries; Engineering; Epidemic; Exposure to; Family Planning; Film; Glycocalyx; Goals; HIV; HIV-1; Human; Human Herpesvirus 2; Leukocytes; Male Genital Organs; Membrane; Methods; Monoclonal Antibodies; Morbidity - disease rate; Nicotiana; Parasites; Prevention; Research; STI prevention; Seminal; Seminal Plasma; Seminal fluid; Sexual Transmission; Sexually Transmitted Diseases; Surveys; Technology; Testing; Transgenic Organisms; Trichomonas; Trichomonas vaginalis; Vagina; Variant; Virus; Virus Diseases; Woman; Zika Virus; antibody engineering; base; experimental study; human monoclonal antibodies; innovation; male; microbicide; mortality; novel; pathogen; prevent; programs; reproductive tract; sperm cell; transmission process; unintended pregnancy; virus envelope

The goal of Project 3 is to determine whether Human Contraception Antibody (HCA) binds to and neutralizes STI pathogens in semen. The rationale behind these experiments is our observation that the male reproductive tract restricted antigen CD52g, which is the target of HCA. inserts via GPI anchor into the plasma membrane of leukocytes and parasites in semen. We hypothesize that HCA will bind to and neutralize HIV infected cells in semen, as well as enveloped viruses that pick up CD52g from infected CD52g-coated cells in the male genital tract. Results of these studies will demonstrate whether HCA has dual activity as a contraceptive agent and STI microbicide. Our Specific Aims are: 1. Determine whether CD52g attaches to seminal leukocytes, STI viruses (HIV-1, HSV-2 and ZIKV) and Trichomonas vaginalis. 2. Determine whether HCA binds to HIV-infected seminal leukocytes, STI viruses and Trichomonas vaginalis. and inhibits their ability to infect target cells. 3. Determine whether seminal leukocytes, viruses and parasites that are coated with CD52g agglutinate with each other or with sperm after treatment with HCA. 4. Determine whether HCA and engineered variants of HCA trap CD52g-coated leukocytes, STI viruses and parasites in cervical mucus (collaboration with Project 2)

项目 3 的目标是确定人类避孕抗体 (HCA) 是否结合并 中和精液中的性传播感染病原体。这些实验背后的基本原理是我们的观察 男性生殖道限制性抗原CD52g是HCA的靶标。插入通过 GPI 锚定在精液中白细胞和寄生虫的质膜中。我们假设 HCA 将结合并中和精液中感染 HIV 的细胞以及包膜病毒 从男性生殖道中感染的 CD52g 包被细胞中拾取 CD52g。这些结果 研究将证明 HCA 是否具有作为避孕药和 STI 的双重活性 杀菌剂。 我们的具体目标是： 1. 确定CD52g是否附着于精液白细胞、STI病毒（HIV-1、HSV-2和 ZIKV）和阴道毛滴虫。 2. 确定 HCA 是否与感染 HIV 的精液白细胞、STI 病毒和 阴道毛滴虫。并抑制它们感染靶细胞的能力。 3. 确定是否有CD52g包被的精液白细胞、病毒和寄生虫 HCA 处理后相互凝集或与精子凝集。 4. 确定 HCA 和 HCA 的工程变体是否捕获 CD52g 包被的白细胞、STI 宫颈粘液中的病毒和寄生虫（与项目 2 合作）