Development and Production of Anti-Malarial Biologicals

疟疾单抗Cis43LS是在VRC发现的，并提供给疫苗生产计划实验室(VPP)。 VPP负责cGMP的生产和监管提交用于临床试验的VRC单抗所需的制造文件。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。VPP扩大了VCMP的能力，包括制造克隆抗体。VPP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。VPP制定了制造CIS43LS所需的制造工艺、最终配方缓冲和分析方法，并将该工艺移交给VCMP用于cGMP生产和产品释放/稳定性测试。VRC于2019年11月获得安全进行，并启动了I期临床试验。由于新冠肺炎大流行，第一阶段的受控人类疟疾感染部分被推迟到2020年10月。此外，2021年5月，在马里启动了用于预防疟疾感染的Cis43LS第二阶段临床试验。注册于2021年8月完成，本次试验的背线结果于2022年3月提供。 对这些生物制品的需求增加了，要求开发小组进一步改进制造工艺和测试方法，以跟上需求。VPP开发了第二种抗疟疾单抗L9LS，导致生产了主细胞库、药物物质、药物产品，并于2021年8月提交了IND申请。在开发过程中，VPP发现单抗在某些缓冲配方中高度稳定，允许VPP比大多数单抗高出50%的L9LS浓度。这使得临床剂量和给药途径在较低的mAb药物产品浓度下是不可能的。L9LS的IND于2021年9月9日获得安全进行，并于10月进行第一阶段研究，10月26日进行受控人类挑战。2022年，马里启动了第二阶段研究，第二阶段研究预计将在肯尼亚开始。

Malaria mAb CIS43LS was discovered at the VRC and provided to the Vaccine Production Program Laboratory (VPP). The VPP 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 VPP expanded the capability of the VCMP to include the manufacture of monoclonal antibodies. The VPP also engages in partnerships and contracts with companies in the vaccine/biotech industry for additional capacity and capability in biologicals manufacturing. The VPP developed the manufacturing process, final formulation buffer, and analytical methods needed for manufacturing the CIS43LS, transferred the process to the VCMP for cGMP production and product release/stability testing. The VRC received safe-to-proceed in November 2019 and initiated Phase I clinical trials. Due to the COVID-19 pandemic, the controlled-human malaria infection part of the Phase I was delayed until October 2020. Additionally, in May of 2021 a Phase II clinical trial was initiated for CIS43LS in Mali for the prevention of malaria infection. Enrollment completed in August of 2021 with topline results from this trial provided in March of 2022. The demand for these biologicals has increased, requiring the development groups to further improve the manufacturing process and test methods to keep up with demand. The VPP developed a second anti-malaria mAb, L9LS, leading to the production of a master cell bank, drug substance, drug product and the filing of an IND in August 2021. During development, The VPP discovered that the mAb was highly stable in certain buffer formulations, allowing for the VPP to concentrate L9LS 50% higher than most mAbs. This allows for clinical dosing and routes of administration that would not have been possible at lower mAb Drug Product concentrations. The IND for L9LS received safe-to-proceed September 9, 2021 and proceed in October for the initial Phase I study with controlled-human challenge October 26th. In 2022, a Phase II study was initiated in Mali and a second one is anticipated to start in Kenya.