AAV Delivered CCR5 Blockade for Prevention of Mother-to-Child HIV Transmission.

项目摘要 由于目前艾滋病毒感染者人数达到历史上最多的水平，阻止艾滋病毒的流行仍然是当务之急。 此外，预防新生儿通过母婴传播感染艾滋病毒仍然是一项重要工作。 在产前保健资源有限地区的主要目标。虽然抗逆转录病毒治疗（ART）已 对于减少HIV-1的传播至关重要，但它并非没有风险，包括ART药物对新生儿的毒性， 耐药病毒变异的发展。因此，迫切需要更安全的预防措施 消除艾滋病毒1的母婴传播。我们已经证明，可以使用CCR 5特异性抗体Leronlimab 作为一种有效的暴露前预防（PrEP）方案在猕猴。在这里，我们建议使用AAV- 载体化的Leronlimab以促进Leronlimab表达在婴儿猕猴中的体内递送以预防围产期 SIV感染。在具体目标1中，我们将确定AAV 9递送的Leronlimab防止获得性免疫应答的能力。 新生猕猴体内的SIV病毒。在目标2中，我们将描述AAV 9基因治疗的长期性能， 给新生猕猴注射这项工作将提供一个安全可行的替代方案，以防止垂直 HIV-1的传播，并支持在婴儿中直接体内递送抗HIV预防性方式。

PROJECT SUMMARY With the most people ever in history currently living with HIV, stopping the HIV epidemic remains imperative. Furthermore, preventing HIV infection in newborns via mother-to-child transmission (MTCT) continues to be a major objective in areas with limited resources for antenatal care. While antiretroviral treatment (ART) has been critical in reducing transmission of HIV-1, it is not without risk, including toxicity of ART drugs in newborns and the development of drug resistant viral variants. Thus, there is an urgent need for safer preventative measures to eliminate MTCT of HIV-1. We have demonstrated that the CCR5-specific antibody Leronlimab can be used as an effective pre-exposure prophylaxis (PrEP) regimen in macaques. Here, we are proposing to utilize AAV- vectored Leronlimab to facilitate in vivo delivery of Leronlimab expression in infant macaques to prevent perinatal SHIV infection. In specific aim 1, we will determine the ability of AAV9-delivered Leronlimab to prevent acquisition of SHIV in newborn macaques. In aim 2, we will characterize the long-term performance of AAV9 gene therapy administered to newborn macaques. This work would provide a safe and viable alternative to prevent vertical transmission of HIV-1 and support direct in vivo delivery of anti-HIV prophylactic modalities in infants.