Preclinical Testing of an Adenoviral Vector based HSV-2 Vaccine

基于腺病毒载体的 HSV-2 疫苗的临床前测试

基本信息

批准号：
7481790
负责人：
C. RICHTER KING
金额：
$ 30万
依托单位：
GENVEC, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7481790
关键词：
Adenovirus Vector Adenoviruses Animal Model Antibodies Antigens Antiviral Therapy Arts Biological Assay CD8B1 gene Capsid Proteins Cellular Immunology Codon Nucleotides Conduct Clinical Trials Dermal Epidemic Frequencies Ganglia Generations Genital system Goals Guanosine Monophosphate HIV Human Human Herpesvirus 2 Immunobiology In Vitro Infection Laboratories Measures Mus Myxoid cyst Neurons Phase Play Pre-Clinical Model Preclinical Testing Proteins Public Health Rate Recombinants Recurrence Risk Role Safety Seeds Seroprevalences Sexual Partners Simplexvirus Skin Small Business Funding Mechanisms Small Business Innovation Research Grant Staging T-Lymphocyte Testing Time Toxicology Vaccines Viral Viral Antigens Virus Shedding base follow-up immunogenicity nonhuman primate novel prevent prototype reactivation from latency research clinical testing response transmission process vector-based vaccine

项目摘要

DESCRIPTION (provided by applicant): This proposal will leverage the expertise in HSV-2 and cellular immunology developed at the UW/FHCRC with the state of the art adenovirus delivery platform developed by GenVec to develop an HSV-2, adenovirus vector based vaccine. This phase 1 SBIR application will generate and test in preclinical models initial prototypes of such a vaccine. The specific aims during phase I of the SBIR are to construct and test two adenovirus vectors each containing a HSV-2 viral antigen, UL-47 and UL-19. These antigens have been shown to cause prevalent in CD4+ and CD8+ T cell responses among humans with naturally acquired HSV-2. It is anticipated that the proposed AdHSV-2 vaccine will increase the HSV-2 specific CD8+ T cell responses to the UL-47 and UL-19 antigens in animal models. During phase II of this SBIR we plan to bring these AdHSV-2 vaccines to the IND stage. The long-term goal of this effort is to conduct clinical trials testing whether AdHSV-2 vaccines decrease acquisition of HSV-2 and/or decrease viral reactivation as measured by frequency and titer of viral shedding and lessened rate of recurrent episodes. PUBLIC HEALTH RELEVANCE: The HSV-2 epidemic has continued to spread throughout the world and seroprevalence rates have climbed to 30-50%. There is a strong association between antecedent HSV-2 infection and increased risk of HIV acquisition. Antiviral therapy to reduce transmission of HSV-2 to sexual partners is only partially successful. No effective HSV-2 vaccine is currently available. Evidence has accumulated on the importance that HSV-2 specific CD8+ T cells play in control of latency and reactivation of HSV-2 infections in humans. Concomitant with these studies of HSV-2 immunobiology has been the recent demonstration in humans that recombinant adenovirus vectors elicit high frequency of HIV CD8+ T cell responses. This proposal will leverage the expertise in HSV-2, and cellular immunology developed in the laboratories of Drs. L. Corey and D. Koelle with the state of the art adenovirus delivery platform developed by GenVec to develop an HSV-2, Ad5 based vaccine.

描述（由申请人提供）：该提案将利用 UW/FHCRC 开发的 HSV-2 和细胞免疫学专业知识以及 GenVec 开发的最先进的腺病毒递送平台来开发基于 HSV-2 腺病毒载体的疫苗。这一阶段 SBIR 应用将生成此类疫苗的初始原型并在临床前模型中进行测试。 SBIR 第一阶段的具体目标是构建和测试两种腺病毒载体，每种载体均含有 HSV-2 病毒抗原 UL-47 和 UL-19。这些抗原已被证明可在自然获得性 HSV-2 患者中引起普遍的 CD4+ 和 CD8+ T 细胞反应。预计所提出的 AdHSV-2 疫苗将增强动物模型中 HSV-2 特异性 CD8+ T 细胞对 UL-47 和 UL-19 抗原的反应。在 SBIR 的第二阶段，我们计划将这些 AdHSV-2 疫苗进入 IND 阶段。这项工作的长期目标是进行临床试验，测试 AdHSV-2 疫苗是否能减少 HSV-2 的获得和/或减少病毒再激活（通过病毒脱落的频率和滴度以及减少复发率来衡量）。公共卫生相关性：HSV-2 疫情继续在全球蔓延，血清阳性率已攀升至 30-50%。既往 HSV-2 感染与 HIV 感染风险增加之间存在密切关联。减少 HSV-2 向性伴侣传播的抗病毒治疗仅取得部分成功。目前尚无有效的 HSV-2 疫苗。越来越多的证据表明，HSV-2 特异性 CD8+ T 细胞在控制人类 HSV-2 感染的潜伏期和重新激活方面发挥着重要作用。与这些 HSV-2 免疫生物学研究相伴随的是，最近在人体中证明重组腺病毒载体可引发高频的 HIV CD8+ T 细胞反应。该提案将利用 HSV-2 和 Drs. 实验室开发的细胞免疫学专业知识。 L. Corey 和 D. Koelle 使用 GenVec 开发的最先进的腺病毒递送平台来开发基于 HSV-2、Ad5 的疫苗。