Production of a Broadly Neutralizing HIV Antibodies

VRC01是几种特殊的广谱中和单抗中的第一种，并被选为人类临床产品。对这种单抗在人体内的测试提供了关于这种单抗提供预防艾滋病毒感染的能力的信息，以及旨在引起类似抗体反应的疫苗是否有望提供类似的预防艾滋病毒感染的保护。VPP通过临床试验材料的产品稳定性支持和库存管理，继续支持VRC01在第二阶段疗效研究AMP中的使用。 VRC的疫苗生产计划实验室(VPP)负责生产cGMP和监管提交VRC单抗进行临床试验所需的制造文件。为了迅速满足其临床试验计划的关键计划需求，VRC开发了一个疫苗试点工厂，称为VCMP(疫苗临床材料计划)，用于生产I/II/III期试验的临床材料。VPPL扩大了VCMP制造单抗的能力。VPPL还与疫苗/生物技术行业的公司建立伙伴关系并签订合同，以增加生物制品制造的能力和能力。VPPL开发制造单抗所需的制造工艺和分析方法，将该工艺移交给VCMP用于cGMP生产和产品释放/稳定性测试。这种方法使VRC能够快速应对新出现的公共卫生威胁，VRC埃博拉治疗性抗体mAb114就是明证，该抗体根据同情使用方案使用，并在2018/19年刚果民主共和国埃博拉扎伊尔疫情的随机对照试验中进行研究。已经开发了许多具有商业价值的单抗(见下文的产品或服务)。随着我们沿着开发道路前进，对这些分子的需求增加了，这要求开发团队进一步改进制造工艺和测试方法，以跟上需求。VPP已经生产了82.5公斤VRC01用于临床试验(第一阶段研究和AMP第二阶段研究)，并生产了一批单抗10E8VLS、N6LS、CAP256LS、VRC01LS和VRC07-523LS。

VRC01 was the first of several exceptionally broadly neutralizing mAbs and was chosen to be produced as a clinical product for human. Testing of this mAb in humans provides information on the ability of this mAb to provide protection from HIV acquisition and as to whether a vaccine designed to elicit a similar antibody response might be expected to provide similar protection from acquisition from HIV. The VPP continued to support the use of VRC01 in the Phase 2 efficacy study, AMP, through product stability support and inventory management of the clinical trial material. Vaccine Production Program Laboratory (VPP) at the VRC is responsible for cGMP production and the manufacturing documentation needed for regulatory submission of VRC mAbs for clinical trials. To expeditiously meet the critical program needs of its Clinical Trials Program, the VRC developed a vaccine pilot plant, known as the VCMP (Vaccine Clinical Materials Program) for the manufacture of clinical materials for Phase I/II/III trials. The VPPL expanded the capability of the VCMP for the manufacture of monoclonal antibodies. The VPPL also engages in partnerships and contracts with companies in the vaccine/biotech industry for additional capacity and capability in biologicals manufacturing. The VPPL develops the manufacturing process and analytical methods needed for manufacturing mAbs, transfers the process to the VCMP for cGMP production and product release/stability testing. Such an approach enables the VRC to rapidly respond to emerging public health threats, as evidenced by the VRCs Ebola therapeutic antibody, mAb114, being used under compassionate use protocols and studied under randomized control trial in the 2018/19 Ebola Zaire outbreak in the Democratic Republic of the Congo. A number of mAbs have been developed that have commercial interest (see Products or Services, below). As we proceed down the development pathway the demand for these molecules has increased requiring the development groups to further improve the manufacturing process and test methods to keep up with demand. The VPP has produced 82.5 kg of VRC01 for clinical trial use (Phase 1 studies and the AMP Phase 2 study) and Phase 1 production lots of the mAbs 10E8VLS, N6LS, CAP256LS, VRC01LS, and VRC07-523LS.