SIV Transmission in Male NHP

描述(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同。已经开展了许多研究来确定艾滋病毒传播的生物学，目的是确定从粘膜病毒传播到远端淋巴组织的过程中可以被疫苗接种中断的阶段。在很大程度上，这项工作的重点是了解艾滋病毒对妇女的传播，而不是通过插入阴茎性交来确定艾滋病毒在暴露于艾滋病毒的男子中的传播和传播。我们最近开发了一种可靠的阴茎艾滋病毒传播模型，使用SIV接种成熟的雄性恒河猴。这个模型概括了艾滋病毒在男性中传播的关键病毒学和流行病学特征，即当接种疫苗放入包皮而不是简单地放在阴茎龟头和阴茎干上时，对男性的传播最有效；在传播后立即在血浆中发现一种病毒变体(Keele，Miller未发表，见初步研究)。我们已经确定了经阴道传播的SIVmac251在恒河猴身上的病毒学和免疫学特征，在这项应用中，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是如何通过阴茎性交传播给男性的，以及作为病毒传播场所的阴茎粘膜表面存在的一系列抗病毒效应机制。这些信息是合理设计疫苗以在男性生殖道引发免疫反应以限制或防止艾滋病毒传播所必需的。

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and shaft of the penis; and a single viral variant is found in plasma immediately after transmission (Keele, Miller Unpublished and see Preliminary Studies).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