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

AAV 提供 CCR5 阻断以预防 HIV 母婴传播。

基本信息

批准号：
10670864
负责人：
Jonah B. Sacha
金额：
$ 21.88万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-25 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10670864
关键词：
Adherence Adult Age Animal Model Animals Antibodies Antibody Therapy Area Binding Blocking Antibodies Breast Feeding Breastfed infant CCR5 gene CD4 Positive T Lymphocytes Characteristics Child Clinical Trials Dependovirus Developing Countries Development Dose Drug Delivery Systems Drug Interactions Epidemic Gene Expression Gene Transduction Agent Growth HIV HIV Infections HIV-1 Health Priorities Human Human Milk Immunoglobulin G Individual Infant Infection Infection Control Infection prevention Injections Intramuscular Macaca Macaca mulatta Mediating Modality Modeling Monitor Mother-to-child HIV transmission Newborn Infant Oral Performance Perinatal Persons Pharmaceutical Preparations Phenocopy Phenotype Plasma Prevention Preventive measure Prophylactic treatment Recording of previous events Regimen Reporting Resistance development Resource-limited setting Resources Risk Route Safety Serious Adverse Event Surface Technology Testing Therapeutic Time Toxic effect Variant Vertical Disease Transmission Vertical Transmission Viral Load result Viral Physiology Virus Work adeno-associated viral vector antenatal care antiretroviral therapy cost delivery vehicle drug development drug resistant virus extracellular gene delivery system gene therapy human disease immunogenic immunogenicity immunoprophylaxis in vivo inhibitor neutralizing antibody novel peripheral blood pre-clinical pre-exposure prophylaxis prevent prophylactic side effect simian human immunodeficiency virus small molecule tissue tropism transgene expression transmission process viral resistance

项目摘要

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.

项目概要由于目前感染艾滋病毒的人数是历史上最多的，因此阻止艾滋病毒流行仍然势在必行。此外，通过母婴传播（MTCT）预防新生儿感染艾滋病毒仍然是一个重要问题。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）已虽然它对于减少 HIV-1 的传播至关重要，但并非没有风险，包括 ART 药物对新生儿和儿童的毒性。耐药病毒变种的发展。因此，迫切需要更安全的预防措施消除 HIV-1 母婴传播。我们已经证明CCR5特异性抗体Leronlimab可以用于作为猕猴有效的暴露前预防 (PrEP) 方案。在这里，我们建议利用 AAV- 载体 Leronlimab 促进 Leronlimab 在婴儿猕猴体内表达，以预防围产期艾滋病毒感染。在具体目标 1 中，我们将确定 AAV9 递送的 Leronlimab 预防获得性感染的能力新生猕猴中的 SHIV 感染。在目标 2 中，我们将描述 AAV9 基因治疗的长期性能给予新生猕猴。这项工作将为防止垂直 HIV-1 传播并支持在婴儿体内直接提供抗 HIV 预防方式。