A Solid-Phase, Long-Acting CCR5 Monoclonal Antibody for HIV Transmission

针对 HIV 传播的固相长效 CCR5 单克隆抗体

• 批准号: 10222531
• 负责人: Jonah B. Sacha
• 金额: $ 93.05万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-23 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10222531
• 关键词: Adherence; Anti-Retroviral Agents; Antibodies; Biopsy; Blocking Antibodies; Blood; CCR5 gene; CXCR4 gene; Chemistry; Clinical; Clinical Trials; Collaborations; Data; Development; Dose; Dose-Limiting; Drug Interactions; Drug Kinetics; Epidemic; Female; Formulation; Foundations; HIV; HIV Antibodies; HIV-1; Half-Life; Health Priorities; Home; Homozygote; Individual; Infection; Injectable; Injections; Length; Macaca; Measurement; Measures; Mediating; Modality; Modeling; Monitor; Monoclonal Antibodies; Mucous Membrane; Oral; PRO 140; Parents; Patients; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Plasma; Preventive vaccine; Reagent; Recording of previous events; Regimen; Resistance; Reverse Transcriptase Inhibitors; Safety; Schedule; Self Administration; Serum; Sexual Transmission; Site; Solid; Techniques; Tenofovir; Testing; Therapeutic; Time; Tissues; Toxic effect; Vaccines; Vagina; Vaginal Ring; Variant; Viral; Virus; antiretroviral therapy; base; compliance behavior; emtricitabine; fight against; global health; high risk; industry partner; male; novel; nucleoside analog; pre-exposure prophylaxis; prevent; prophylactic; receptor; rectal; rectal HIV transmission; sexual HIV transmission; side effect; simian human immunodeficiency virus; subcutaneous; success; transmission process; user-friendly; vaginal transmission; viral resistance; weapons

PROJECT SUMMARY With 36 million people currently living with HIV worldwide and no vaccine currently available, developing a pre- exposure prophylactic (PREP) HIV regimen that protects against sexual transmission remains a top global health priority. Recently, a CCR5 blocking monoclonal antibody, Leronlimab, has shown exceptional safety, tolerability, and anti-HIV activity in multiple clinical trials. Given that sexual transmission of HIV is almost exclusively mediated by CCR5-tropic variants, Leronlimab may be extremely effective as a PREP reagent. We confirmed the ability of once-weekly administered Leronlimab to protect macaques from rectal transmission of CCR5-tropic SHIV. However, a once-quarterly at home formulation would dramatically increase patient adherence. To this end we will develop a novel formulation of long-acting Leronlimab that can be administered at home in a low volume able to provide coverage for three months. In specific aim 1, we will determine the pK and receptor occupancy of this new Leronlimab formulation in blood and tissue sites of sexual transmission. In specific aim 2, we will determine the length of time a single injection at the clinical dose can protect both male and female macaques against rectal transmission. In specific aim 3, we will determine the length of time a single injection of the clinical dose can protect against vaginal transmission in cycling female macaques. These studies will determine the optimal clinical dosing of long-acting Leronlimab and lay the foundation for testing long-acting Leronlimab clinically as PREP in individuals at high-risk of acquiring HIV via sexual transmission.

项目总结