Modifications to improve HIV neutralizing antibodies

改进 HIV 中和抗体的修饰

• 批准号: 8946603
• 负责人: John Mascola
• 金额: $ 180万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8946603
• 关键词: Affinity; Antibodies; Cells; Goals; HIV; HIV Infections; HIV-1; Half-Life; Human; Modification; Monoclonal Antibodies; Mutation; Patients; Relative (related person); Structure; Testing; Treatment Efficacy; Virus; Work; base; design; immunogenicity; improved; in vivo; in vivo Model; neutralizing antibody

This work describes targeted mutations applied to several HIV-1 neutralizing antibodies that have been isolated from HIV+ donors. The mutations are designed to increase breadth, potency and half-life to improve potential efficacy for therapeutic application and to decrease immunogenicity to allow for more effective and longer lasting in vivo function. There are also structure-based mutations designed to improve affinity and neutralization potency, which are based on the crystal structures. These modifications are tested against a panel of HIV-1 viruses to determine the breadth and strength of their ability to neutralize. The most potent of these candidates are then selected for testing in in vivo models with the long term goal of testing in humans. In addition, bi-specific antibodies are being developed with the goal of targeting and treating reservoirs of HIV infection in cells.

这项工作描述了用于从HIV+供体分离的几种HIV-1中和抗体的靶向突变。 该突变旨在提高宽度，效力和半衰期，以提高治疗应用的潜在疗效，并降低免疫原性，以使体内功能更有效，更持久。 也有基于结构的突变旨在提高基于晶体结构的亲和力和中和效力。 这些修饰是针对HIV-1病毒小组测试的，以确定它们中和的能力的广度和强度。 然后选择最有效的候选物进行在体内模型中进行测试，其长期目标是在人类中进行测试。 此外，正在开发双特异性抗体，目的是靶向和治疗细胞中HIV感染的储层。