Modifications to improve HIV neutralizing antibodies

这项工作描述了应用于从HIV+捐赠者分离的几种HIV-1中和抗体的定向突变。这些突变旨在增加广度、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，以实现更有效和更持久的体内功能。也有基于结构的突变，旨在提高亲和力和中和效力，这是基于晶体结构的。这些修改针对一组HIV-1病毒进行测试，以确定它们中和能力的广度和强度。然后选择这些候选中最有效的在活体模型中进行测试，长期目标是在人体上进行测试。此外，正在开发双特异性抗体，目标是靶向和治疗细胞中艾滋病毒感染的宿主。

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.