GM-CSF-Adjuvanted Clade C DNA/MVA and MVA/MVA Vaccines

GM-CSF 佐剂 C 分支 DNA/MVA 和 MVA/MVA 疫苗

• 批准号: 7269092
• 负责人: HARRIET L ROBINSON
• 金额: $ 291.51万
• 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: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269092
• 关键词: GM; CSF; Adjuvanted; Clade; DNA

DESCRIPTION (provided by applicant): 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 DNA 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 DNA and MVA vaccines are mature products that 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. Dr. Harriet Robinson, the program director, has effectively led the development of the vaccines in this IPCAVD during a long-term collaboration between her laboratory at the Emory Vaccine Center, Dr. Bernard Moss's laboratory at the NIAID and Dr. Tom Folks' group at the US Centers for Disease Control. In 2004, GeoVax Inc. of Atlanta GA licensed the technology for the vaccines and entered into an inter-institutional agreement between Emory, NIAID, and CDC for further development and commercialization of the vaccines. This IPCAVD has been submitted by GeoVax where Dr. Robinson plans to move in the spring of 2007 to work full time on the development and translation of the vaccines that she and her team have developed. This IPCAVD has 3 projects and 2 cores. Dr. Mark Keister of GeoVax (P.I.) with Dr. Robinson as co-P.I. (at GeoVax) will lead the project developing and manufacturing immunogens. Dr. Rama Amara (at Emory) will lead preclinical studies in the SIV251/rhesus macaque model. Dr. Mark Mulligan (at Emory) will lead the project on clinical trials (conducted through the HVTN) with Dr. Robinson as co-Pi (at GeoVax) overseeing the conduct of ancillary immunogenicity assays. Dr. Robinson (at GeoVax) will lead the administrative core. Dr. Pamela Kozlowski will lead a mucosal Ab core at Harvard University. Critical decisions will be supported by both Internal and External Advisory Committees. A strength of this IPCAVD is its leadership by a private/public/academic/industrial team with demonstrated ability to conduct a focused vaccine development program to bring promising products to clinical trials and commercialization. PROJECT 1: PROJECT DEVELOPMENT AND MANFACTURE (Hildebrand, D.) PROJECT 1 DESCRIPTION (provided by applicant): 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 DNA 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 DNA 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.

描述（由申请人提供）：HIV-1引起的可获得的免疫缺陷综合症（AIDS）是非洲的主要死亡原因，也是全球死亡的第四个主要原因。该IPCAVD正在开发使用DNA进行启动的艾滋病毒/艾滋病疫苗，将MVA和MVA用于（DNA/MVA疫苗），以及更简单，最终更容易部署这些疫苗的形式，将MVA用于启动和增强（MVA/MVA疫苗）。 DNA和MVA疫苗都是成熟的产品，它们使用单​​个矢量表达像颗粒一样的病毒（VLP）。此IPCAVD试图将GM-CSF（辅助）（辅助）构建到这些产品中，以在顺式中表达。在临床前研究中，GM-CSF的共表达显着增强了保护。 IPCAVD的一个中心假设是GM-CSF通过增强引起的T细胞和AB反应的粘膜存在来改善保护。在南部非洲和亚洲部分地区流行的进化枝C HIV-1占全球感染的一半，占印度案例的90％，这个国家迅速传播了感染，在其总案例中已经超过了南非。 IPCAVD的疫苗开发工作重点是为印度开发进化枝C疫苗。 计划主管哈里特·罗宾逊（Harriet Robinson）博士在她在埃默里疫苗中心的实验室，尼亚德（Niaid）的伯纳德·莫斯（Bernard Moss）博士和美国疾病控制中心的汤姆·洛克斯（Tom Folks）小组的实验室长期合作期间，有效地领导了该IPCAVD的疫苗开发。 2004年，亚特兰大GA的Geovax Inc.许可了该疫苗的技术，并签订了Emory，Niaid和CDC之间的机构间协议，以进一步开发和商业化疫苗。该IPCAVD由Geovax提交，Robinson博士计划在2007年春季搬家，以全职开发和翻译她和她的团队开发的疫苗。 该IPCAVD有3个项目和2个核心。 Geovax（P.I.）的Mark Keister博士与Robinson博士一起担任Co-P.I。 （在Geovax）将领导该项目开发和制造免疫原子。 Rama Amara博士（在Emory）将在SIV251/Rhesus Macaque模型中领导临床前研究。马克·穆里根（Mark Mulligan）博士（在埃默里（Emory））将以鲁滨逊博士为临床试验（通过HVTN进行）作为Co-Pi（Geovax）（在Geovax上）负责监督辅助免疫原性测定的行为。罗宾逊博士（在Geovax）将领导行政核心。帕梅拉·科兹洛夫斯基（Pamela Kozlowski）博士将领导哈佛大学的粘膜腹部核心。关键决定将得到内部和外部咨询委员会的支持。 IPCAVD的优势在于其由私人/公共/学术/工业团队的领导才能，其能力有能力进行集中的疫苗开发计划，以将有希望的产品带入临床试验和商业化。 项目1：项目开发和人类事件（Hildebrand，D。） 项目1描述（由申请人提供）：由HIV-1引起的可获得的免疫缺陷综合征（AIDS）是非洲死亡的主要原因，也是全球第四大死亡原因。该IPCAVD正在开发使用DNA进行启动的艾滋病毒/艾滋病疫苗，将MVA和MVA用于（DNA/MVA疫苗），以及更简单，最终更容易部署这些疫苗的形式，将MVA用于启动和增强（MVA/MVA疫苗）。 DNA和MVA疫苗都使用单载体来表达像颗粒一样的病毒（VLP）。该IPCAVD试图将GM-CSF（辅助）（辅助）构建到这些产物中以在顺式中表达。在临床前研究中，GM-CSF的共表达显着增强了保护。 IPCAVD的一个中心假设是GM-CSF通过增强引起的T细胞和AB反应的粘膜存在来改善保护。在南部非洲和亚洲部分地区流行的进化枝C HIV-1占全球感染的一半，占印度案例的90％，这个国家迅速传播了感染，在其总案例中已经超过了南非。 IPCAVD的疫苗开发工作重点是为印度开发进化枝C疫苗。 该制造项目具有五个具体目标： *疫苗载体开发。 *评估疫苗向量的适用性。 * CGMP合同的制造和毒理学测试疫苗向量。 *对HVTN 1期试验的监管支持。 *开发和行为释放和稳定性测定。 该项目将由Mark Keister博士领导，并由Harriet Robinson博士共同执导。伯纳德·莫斯（Bernard Moss）博士将根据GEOVAX，EMORY，CDC和NIAID之间开发DNA/MVA和MVA/MVA疫苗的建设协议。