Next Generation Development of Broadly Neutralizing HIV Antibodies for Prevention

用于预防的下一代广泛中和艾滋病毒抗体的开发

• 批准号: 10199732
• 负责人: TIMOTHY FOUTS
• 金额: $ 47万
• 依托单位: ADVANCED BIOSCIENCE LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-09 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10199732
• 关键词: AIDS prevention; Adherence; Antibodies; Binding Sites; Clinical Research; Clinical Trials; Development; Epitopes; Future; HIV; HIV Antibodies; HIV Vaccine Trials Network; HIV envelope protein; Half-Life; Life Extension; Monoclonal Antibodies; Mutation; Pharmaceutical Preparations; Prevention; Preventive measure; Regimen; cGMP production; improved; neutralizing antibody; next generation; stability testing

HIV broadly neutralizing antibodies (bnAbs) are currently being evaluated in clinical trials for both HIV treatment and prevention indications - including VRC01, a CD4-binding site monoclonal antibody (bnMAb), in the current AMP clinical trial HVTN 704/HPTN 085. Current studies indicate that 2 or more bnAbs targeting different epitopes will probably be needed for successful treatment and prevention regimens. PGDM1400 and PGT121 are two bnAbs that recognize unique epitopes on the HIV envelope protein and could be used in addition to VRC01 for coverage. Clinical trials are currently evaluating these antibodies; however, the current clinical trial material for these antibodies do not have half-life extension mutations that would greatly improve their half-life and mitigate adherence issues commonly seen with current ART and preventative measures.

HIV广泛中和抗体（bnAbs）目前正在HIV治疗和预防适应症的临床试验中进行评估，包括目前AMP临床试验HVTN 704/HPTN 085中的cd4结合位点单克隆抗体VRC01 （bnMAb）。目前的研究表明，成功的治疗和预防方案可能需要2种或更多针对不同表位的bnab。PGDM1400和PGT121是两种识别HIV包膜蛋白上独特表位的bnAbs，可以与VRC01一起用于覆盖。临床试验目前正在评估这些抗体；然而，目前这些抗体的临床试验材料没有半衰期延长突变，这将大大改善它们的半衰期，减轻当前抗逆转录病毒治疗和预防措施中常见的依从性问题。