Development and Production of HIV Vaccines and Adjuvants

HIV-1疫苗旨在赋予对多种HIV毒株的免疫力，将在VPP开发，通过VCMP按照现行的良好生产规范（cGMP）生产用于人体临床试验，并发布用于健康人类志愿者的人体临床试验。这些疫苗可通过诱导可中和多种HIV分离株的抗体而赋予广泛免疫。如果这些临床试验证明疫苗的安全性和免疫原性，可能会在更大规模的（第2阶段）试验中进行进一步评估，这将需要更大规模地生产临床试验材料。VPP正在开发的疫苗包括基于稳定Env三聚体的蛋白质亚基和HIV融合肽与破伤风类毒素重组片段的偶联物。蛋白质亚单位疫苗的免疫原性可以通过与疫苗共同施用佐剂而得到改善，明矾和碳磷脂佐剂都已生产出来供人使用，并正在进行临床试验。VPP和VCMP之间的联合开发导致了2021年生产的Adjuplex的工艺和灭菌过程的技术转让，目前正在与以前生产的艾滋病毒疫苗进行临床试验测试；Trimer 4571， Trimer 6931和FP8-rTTHC。目前正在开发新的艾滋病毒疫苗，包括FP7-rTTHC、FP6-rTTHC和Trimer 7678。FP6和FP7疫苗将于2022年晚些时候在VCMP生产，而Trimer 7678将于2023年初生产。

HIV-1 vaccines designed to confer immunity against multiple strains of HIV will be developed at the VPP, manufactured through the VCMP for human clinical trials in compliance with current Good Manufacturing Practices (cGMP) and released for use in human clinical trials in healthy human volunteers. These vaccines may confer broad immunity as defined by inducing antibodies that may neutralize multiple HIV isolates. If these clinical trials demonstrate safety and immunogenicity of the vaccines, further evaluation may take place in larger (Phase 2) trials which will necessitate production of the clinical trial materials at larger scale. Vaccines under development at the VPP include protein subunits based on stabilized Env trimers and conjugates of the HIV fusion peptide to a recombinant fragment of the tetanus toxoid. The immunogenicity of protein subunit vaccines can be improved with the use of adjuvants co-administered with the vaccines, and both alum and Carbopol-lecithin adjuvants have been produced for human use and undergoing testing in clinical trials. Joint development between the VPP and VCMP has led to technology transfer of the process and sterilization process of Adjuplex which was manufactured in 2021 and currently undergoing testing in a clinical trial with previously manufactured HIV vaccines; Trimer 4571, Trimer 6931, and FP8-rTTHC. Development is ongoing for new HIV Vaccines including FP7-rTTHC, FP6-rTTHC, and Trimer 7678. The FP6 and FP7 vaccines will be manufactured at the VCMP later in 2022, while Trimer 7678 will be manufactured in early 2023.