Product Development and Manufacture

产品开发与制造

• 批准号: 7280621
• 负责人: Mark W Reynolds
• 金额: $ 120.3万
• 依托单位: GEOVAX, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7280621
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Adjuvant; Africa; Agreement; Antigens; Asia; Biological; Biological Assay; Cause of Death; Cell Line; Centers for Disease Control and Prevention (U.S.); Clinical Trials; Communication; Condition; Contracts; Country; Cyclic GMP; DNA; DNA Vaccines; DNA/MVA vaccine; Data; Development; Facility Construction Funding Category; Fermentation; Gene Expression; Genetic; Genetic Engineering; Genetic screening method; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; HIV-1; Human; Immune response; Immunity; India; Infection; Institutes; Laboratory Personnel; Mosses; National Institute of Allergy and Infectious Disease; Numbers; Phase I Clinical Trials; Process; Production; Recombinants; Regulatory Affairs; Research Contracts; Safety; Sensitivity and Specificity; South Africa; Southern Africa; T-Lymphocyte; Testing; Toxicology; United States Food and Drug Administration; Vaccines; Virus; Virus-like particle; Work; blastomere structure; concept; doxorubicin/mitomycin/vinblastine protocol; immunogenicity; improved; manufacturing process; new technology; novel vaccines; pre-clinical; preclinical study; programs; response; symposium; vaccine development; vaccine evaluation; vector; vector vaccine

The acquired immunodeficiency syndrome (AIDS) caused by HIV-1 is the leading cause of death in Africa and the fourth leading cause of death worldwide. This IPCAVD is developing HIV/AIDS vaccines that use DMA for priming and MVA for boosting (DNA/MVA vaccine) as well as a simpler and ultimately easier to deploy form of these vaccines, the use of MVA for both priming and boosting (MVA/MVA vaccine). Both the DMA and MVA vaccines use single vectors to express virus like particles (VLP). This IPCAVD seeks to build GM-CSF, an adjuvant, into these products for expression in cis. In preclinical studies, co-expression of GM-CSF has substantially enhanced protection. A central hypothesis for the IPCAVD is that GM-CSF improves protection by enhancing the mucosal presence of elicited T cell and Ab responses. Clade C HIV-1 which is endemic in southern Africa and parts of Asia accounts for about one half of the infections worldwide and >90% of the cases in India, a country with a rapidly spreading infection that has surpassed South Africa in its total number of cases. The vaccine development effort of this IPCAVD is focused on developing a clade C vaccine for India. This manufacturing project has five specific aims: ¿ Vaccine vector development. ¿ Assessment of vaccine vectors for suitability for manufacture. ¿ cGMP contract manufacture and toxicology testing of vaccine vectors. ¿ Regulatory support for an HVTN phase 1 trial. ¿ Development and conduct of release and stability assays. The project will be led by Dr. Mark Keister and co-directed by Dr. Harriet Robinson. Construction of the needed MVA vector will be by Dr. Bernard Moss under an Inter-Institutional Agreement for the development of DNA/MVA and MVA/MVA vaccines between GeoVax, Emory, CDC and the NIAID.

由 HIV-1 引起的获得性免疫缺陷综合症 (AIDS) 是人类死亡的主要原因 非洲和全球第四大死因 该 IPCVD 正在开发艾滋病毒/艾滋病疫苗。 使用 DMA 进行初免并使用 MVA 进行加强（DNA/MVA 疫苗）以及更简单且最终的疫苗 这些疫苗更容易部署，使用 MVA 进行初免和加强（MVA/MVA DMA 和 MVA 疫苗都使用单个载体来表达病毒样颗粒 (VLP)。 该 IPCAVD 旨在将 GM-CSF（一种佐剂）构建到这些产品中以顺式表达。 临床前研究表明，GM-CSF 的共表达显着增强了保护作用。 IPCVD 的假设是 GM-CSF 通过增强粘膜存在来改善保护作用 引起 T 细胞和抗体反应，C 型 HIV-1 在南部非洲和亚洲部分地区流行。 约占全球感染病例的一半，而印度感染病例的 90% 以上是由该病引起的。 感染迅速蔓延，病例总数已超过南非。 该 IPCVD 的开发工作重点是为印度开发 C 分支疫苗。 该制造项目有五个具体目标： ¿疫苗载体的开发。 ¿评估疫苗载体的生产适用性。 ¿疫苗载体的 cGMP 合同生产和毒理学测试。 ¿对 HVTN 第一阶段试验的监管支持。 ¿释放和测定稳定性的开发和实施。 该项目将由 Mark Keister 博士领导，并由 Harriet Robinson 博士共同指导。 所需的 MVA 载体将由 Bernard Moss 博士根据一项机构间协议提供 GeoVax、埃默里大学、CDC 和 NIAID 之间开发 DNA/MVA 和 MVA/MVA 疫苗。