Core--Vector

载体核心设施(核心B)将为IPCAVD赠款中描述的临床前研究和临床试验生产所有重组腺病毒(Rad)疫苗。 Crucell Holland BV是一家中型生物技术公司，致力于传染病疫苗的开发。特别是，Crucell率先开发了基于Rad载体的疫苗，并从几种在人类群体中具有低血清阳性率的Ad血清型开发了疫苗载体。Crucell也一直是基于Rad载体的疫苗从临床前到临床转化开发的领导者。特别是，Crucell开发了强大的生产和纯化方法来生产符合所有FDA和EC要求的临床级Rad疫苗，标准化和验证释放试验，并开发了几种包装细胞系，以支持 制药规模的制造。集中的生产、纯化和质量控制标准对于确保基于载体的Rad载体的质量至关重要，该载体将用于IPCAVD赠款中的疫苗研究。该核心设施将生产研究级Rad疫苗，以支持项目1和2中描述的临床前研究，并生产临床级Rad疫苗，以支持项目2中描述的临床试验。我们为该核心设施提出以下三个具体目标：1.制造、纯化和质量控制表达HIV-1和SIV抗原的研究级Rad疫苗；2.在良好的制造规范(GMP)和良好的实验室规范(GLP)条件下制造、纯化、质量控制和发布表达HIV-1抗原的临床级Rad疫苗；3.协调GLP条件下的临床前毒理学研究，并准备IND申请，以支持I期和II期临床试验的启动。

The Vector Core Facility (Core B) will manufacture all the recombinant adenovirus (rAd) vaccines for the preclinical studies and the clinical trials described in this IPCAVD grant. Crucell Holland BV is a medium-sized biotechnology company that is dedicated to the development of vaccines for infectious diseases. In particular, Crucell has pioneered the development of rAd vector-based vaccines and has developed vaccine vectors from several Ad serotypes that have low seroprevalence in human populations. Crucell has also been a leader in the preclinical-to-clinical translational development of rAd vector-based vaccines. In particular, Crucell has developed robust production and purification methods to manufacture clinical-grade rAd vaccines that conform to all FDA and EC requirements, standardized and validated release assays, and developed several packaging cell lines that support pharmaceutical-scale manufacturing. Centralized production, purification, and quality control standards are critical to ensure the quality of the rAd vector-based vectors that will be used in the vaccine studies in this IPCAVD grant. This Core Facility will produce the research-grade rAd vaccines to support the preclinical studies described in Projects 1 and 2 and the clinical-grade rAd vaccines to support the clinical trials described in Project 2. We propose the following three Specific Aims for this Core Facility: 1. To manufacture, purify, and quality control research-grade rAd vaccines expressing HIV-1 and SIV antigens; 2. To manufacture, purify, quality control, and release clinical-grade rAd vaccines expressing HIV-1 antigens under Good Manufacturing Practice (GMP) and Good Laboratory Practice (GLP) conditions; and 3. To coordinate preclinical toxicology studies under GLP conditions and prepare IND applications to support the initiation of phase I and phase II clinical trials.