SIV Transmission in Male NHP

男性 NHP 中的 SIV 传播

• 批准号: 8116341
• 负责人: CHRISTOPHER James MILLER
• 金额: $ 72.35万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116341
• 关键词: AIDS Vaccines; Abdomen; Animals; Antiviral Agents; Biology; Biology of HIV Transmission; Blood; Cells; Chest; Dendritic Cells; Distal; Distant; Epidemiology; Female; Genital system; Glans penis; Goals; HIV; HIV Infections; Heterosexuals; Immune; Immune response; Immunology; Infection; Lead; Lymphatic vessel; Lymphoid Tissue; Macaca mulatta; Male Genital Organs; Modeling; Monkeys; Organ; Pathway interactions; Patients; Plasma; Process; SIV; Site; Staging; Stream; Surface; T-Lymphocyte; Tissues; Urethra; Vaccination; Vaccine Design; Vaccines; Variant; Viral; Virion; Virus; Woman; base; high risk men; lymph nodes; male; men; penis; penis foreskin; preclinical study; prevent; transmission process; virology

DESCRIPTION (provided by applicant): HIV is primarily transmitted by heterosexual contact and approximately equal numbers of men and women are infected with the virus worldwide. Numerous studies to define the biology of HIV transmission have been undertaken with the goal of identifying stages in the processes from mucosal virus transmission through dissemination to distal lymphoid tissues that can be interrupted by vaccination. To large extent this effort has focused on understanding transmission of HIV to women with little effort define the transmission and dissemination in men exposed to HIV by insertive penile intercourse. We recently developed a reliable model of penile HIV transmission using SIV inoculation of mature male rhesus macaques. This model recapitulates the key virologic and epidemiologic features of HIV transmission in men, i.e. transmission is most efficient in to males when the inoculum is placed into the foreskin rather than simply onto the glans and shaft of the penis; and a single viral variant is found in plasma immediately after transmission (Keele, Miller Unpublished and see Preliminary Studies). We have characterized the virology and immunology of vaginally transmitted SIVmac251 in rhesus monkeys and in this application we propose to conduct parallel studies of penile SIV transmission. The studies will lead to a better understanding of how the HIV is transmitted to males by penile intercourse and the range of antiviral effector mechanisms that are present in the penile mucosal surfaces that are the sites of virus transmission. This information is required to rationally design vaccines to elicit immune responses in the male genital tract that can limit or prevent HIV transmission PUBLIC HEALTH RELEVANCE (provided by applicant): Men are regularly infected by penile HIV transmission and the foreskin seems to be a critical target tissue, because uncircumcised men are at higher risk for HIV infection. Despite this, almost nothing is known about the biology of penile HIV transmission. By defining the virology and immunology of SIV in the male genital we will be provide the biologic basis for attempting to elicit immune responses in these tissues by vaccines.

描述（由申请人提供）：艾滋病毒主要通过异性接触传播，全世界感染该病毒的男性和女性人数大致相等。已经进行了大量的研究来定义艾滋病毒传播的生物学，目的是确定从粘膜病毒传播到传播到远端淋巴组织的过程中的各个阶段，这些阶段可以通过疫苗接种来中断。在很大程度上，这项工作的重点是了解艾滋病毒向女性的传播，而很少努力定义通过插入阴茎性交接触艾滋病毒的男性的传播和传播。我们最近通过对成熟雄性恒河猴进行 SIV 接种，开发了一种可靠的阴茎 HIV 传播模型。该模型概括了男性艾滋病毒传播的关键病毒学和流行病学特征，即当接种物放入包皮而不是简单地置于龟头和阴茎干时，男性的传播效率最高；传播后立即在血浆中发现单一病毒变体（Keele、Miller 未发表并参见初步研究）。我们已经对恒河猴中阴道传播的 SIVmac251 的病毒学和免疫学进行了表征，在此应用中，我们建议对阴茎 SIV 传播进行平行研究。这些研究将有助于更好地了解艾滋病毒如何通过阴茎性交传播给男性，以及作为病毒传播部位的阴茎粘膜表面存在的一系列抗病毒效应机制。需要这些信息来合理设计疫苗，以在男性生殖道中引发免疫反应，从而限制或预防艾滋病毒传播 公共卫生相关性（由申请人提供）：男性经常通过阴茎传播艾滋病毒，包皮似乎是一个关键的目标组织，因为未受割礼的男性感染艾滋病毒的风险更高。尽管如此，人们对阴茎艾滋病毒传播的生物学几乎一无所知。通过定义男性生殖器中 SIV 的病毒学和免疫学，我们将为尝试通过疫苗在这些组织中引发免疫反应提供生物学基础。