Development and Production of HIV Vaccines and Adjuvants

VPP将开发旨在对多种HIV毒株产生免疫力的HIV-1疫苗，根据当前的良好制造规范(CGMP)，通过VCMP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。这些疫苗可以通过诱导中和多种HIV分离株的抗体来产生广泛的免疫力。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(第二阶段)试验中进行进一步的评估，这将需要更大规模的临床试验材料的生产。VPP正在开发的疫苗包括基于稳定的环境三聚体的蛋白质亚单位和艾滋病毒融合肽与破伤风类毒素的重组片段的结合物。蛋白亚单位疫苗的免疫原性可以通过使用与疫苗共同给予的佐剂来改善，明矾和Carbopol-卵磷脂佐剂都已经生产出来供人类使用，或正在开发用于后续的GMP生产。VPP和VCMP之间的联合开发导致了Adjuplex工艺和灭菌工艺的技术转让，Adjuplex将于2021年晚些时候生产，并用于以前制造的艾滋病毒疫苗的临床试验；Trimer 4571、Trimer 6931和FP8-rTTHC。

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 or are in development for subsequent GMP production. Joint development between the VPP and VCMP has led to technology transfer of the process and sterilization process of Adjuplex which will be manufactured later in 2021 and used in a clinical trial with previously manufactured HIV vaccines; Trimer 4571, Trimer 6931, and FP8-rTTHC.