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: 8132550
• 负责人: HARRIET L ROBINSON
• 金额: $ 435.23万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8132550
• 关键词: GM; CSF; Adjuvanted; Clade; DNA

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.

由 HIV-1 引起的获得性免疫缺陷综合症 (AIDS) 是非洲的首要死因，也是全球第四大死因。该 IPCAVD 正在开发使用 DNA 进行初免和 MVA 进行加强的 HIV/艾滋病疫苗（DNA/MVA 疫苗），以及这些疫苗的更简单且最终更容易部署的形式，即使用 MVA 进行初免和加强（MVA/MVA 疫苗）。 MVA 疫苗）。 DNA疫苗和MVA疫苗都是使用单一载体表达病毒样颗粒（VLP）的成熟产品。本IPCAVD旨在将GM-CSF这种佐剂构建到这些产品中以顺式表达。在临床前研究中，GM-CSF 的共表达显着增强了保护作用。 IPCAVD 的一个中心假设是 GM-CSF 通过增强引起的 T 细胞和抗体反应的粘膜存在来改善保护。 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，占印度病例的 90% 以上，该国感染传播迅速，感染总数已超过南非案例数。该 IPCVD 的疫苗开发工作重点是为印度开发 C 分支疫苗。 项目主任 Harriet Robinson 博士在埃默里疫苗中心的实验室、NIAID 的 Bernard Moss 博士的实验室和 Tom Folks 博士的小组之间的长期合作中，有效地领导了该 IPCAVD 中疫苗的开发在美国疾病控制中心。 2004 年，佐治亚州亚特兰大的 GeoVax Inc. 获得了疫苗技术许可，并与埃默里大学、NIAID 和 CDC 签订了机构间协议，以进一步开发和商业化疫苗。该 IPCAVD 已由 GeoVax 提交，Robinson 博士计划于 2007 年春天搬到 GeoVax，全职从事她和她的团队开发的疫苗的开发和翻译工作。 这个IPCAVD有3个项目和2个核心。 GeoVax 的 Mark Keister 博士（P.I.）和 Robinson 博士担任联合 P.I. （GeoVax）将领导该项目开发和制造免疫原。 Rama Amara 博士（埃默里大学）将领导 SIV251/恒河猴模型的临床前研究。 Mark Mulligan 博士（埃默里大学）将领导该临床试验项目（通过 HVTN 进行），Robinson 博士将担任联合 Pi（GeoVax 大学），监督辅助免疫原性测定的进行。 Robinson 博士（GeoVax）将领导行政核心。 Pamela Kozlowski 博士将领导哈佛大学的粘膜抗体核心团队。关键决策将得到内部和外部咨询委员会的支持。该 IPCVD 的优势在于其由私人/公共/学术/工业团队领导，该团队已证明有能力开展有针对性的疫苗开发计划，将有前途的产品带入临床试验和商业化。

项目成果

Local control of repeated-dose rectal challenges in DNA/MVA-vaccinated macaques protected against a first series of simian immunodeficiency virus challenges.

对 DNA/MVA 疫苗接种的猕猴进行重复剂量直肠攻击的局部控制可抵御第一系列猿猴免疫缺陷病毒的攻击。

• 发表时间: 2014-05
• 作者: Kannanganant, Sunil;Gangadhara, Salaija;Lai, Lilin;Lawson, Benton;Kozlowski, Pamela A;Robinson, Harriet L;Amara, Rama Rao
• 通讯作者: Amara, Rama Rao

Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.

GEO-D03 DNA 疫苗共表达 HIV-1 病毒样颗粒和粒细胞-巨噬细胞集落刺激因子。

• 发表时间: 2012-11-01
• 影响因子: 4.8
• 作者: Hellerstein, Michael;Xu, Yongxian;Marino, Tracie;Lu, Shan;Yi, Hong;Wright, Elizabeth R;Robinson, Harriet L
• 通讯作者: Robinson, Harriet L

Non-neutralizing antibodies in prevention of HIV infection.

非中和抗体预防艾滋病毒感染。

• 发表时间: 2013-02
• 影响因子: 4.6
• 作者: Robinson; Harriet L
• 通讯作者: Harriet L

O-mannosylation of the Mycobacterium tuberculosis adhesin Apa is crucial for T cell antigenicity during infection but is expendable for protection.

结核分枝杆菌粘附素 Apa 的 O-甘露糖基化对于感染期间的 T 细胞抗原性至关重要，但对于保护来说是可消耗的。

• 发表时间: 2013
• 影响因子: 6.7
• 作者: Nandakumar, Subhadra;Kannanganat, Sunil;Dobos, Karen M;Lucas, Megan;Spencer, John S;Fang, Sunan;McDonald, Melissa A;Pohl, Jan;Birkness, Kristin;Chamcha, Venkateswarlu;Ramirez, Melissa V;Plikaytis, Bonnie B;Posey, James E;Amara, Rama Rao;Sabl
• 通讯作者: Sabl

Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine.

脱氧核糖核酸/改良痘苗安卡拉猴免疫缺陷病毒疫苗可产生强效但与年龄相关的保护。

• 发表时间: 2016-01
• 影响因子: 4.2
• 作者: Chamcha, Venkateswarlu;Kannanganat, Sunil;Gangadhara, Sailaja;Nabi, Rafiq;Kozlowski, Pamela A;Montefiori, David C;LaBranche, Celia C;Wrammert, Jens;Keele, Brandon F;Balachandran, Harikrishnan;Sahu, Sujata;Lifton, Michelle;Santra, Sampa;Basu
• 通讯作者: Basu