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

• 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
• 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

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）：本提案将利用UW/FHCRC开发的HSV-2和细胞免疫学专业知识以及GenVec开发的最新腺病毒递送平台，开发基于HSV-2腺病毒载体的疫苗。SBIR的第一阶段应用将在临床前模型中生成并测试这种疫苗的初始原型。SBIR第一阶段的具体目标是构建和测试两种腺病毒载体，每种载体含有HSV-2病毒抗原UL-47和UL-19。这些抗原已显示在具有天然获得性HSV-2的人类中引起普遍的CD 4+和CD 8 + T细胞应答。预期所提出的AdHSV-2疫苗将增加动物模型中HSV-2特异性CD 8 + T细胞对UL-47和UL-19抗原的应答。在SBIR的第二阶段，我们计划将这些AdHSV-2疫苗带入IND阶段。这项工作的长期目标是进行临床试验，测试AdHSV-2疫苗是否减少HSV-2的获得和/或减少病毒再活化，通过病毒脱落的频率和滴度以及复发率的降低来测量。 公共卫生相关性：HSV-2流行病继续在世界各地蔓延，血清阳性率已攀升至30- 50%。有一个很强的关联之间的先行HSV-2感染和艾滋病毒感染的风险增加。减少HSV-2向性伴侣传播的抗病毒治疗仅部分成功。目前还没有有效的HSV-2疫苗可用。已经积累了关于HSV-2特异性CD 8 + T细胞在控制人类HSV-2感染的潜伏期和再活化中起重要作用的证据。伴随着HSV-2免疫生物学的这些研究，最近在人类中证实重组腺病毒载体引起高频率的HIV CD 8 + T细胞应答。该提案将利用HSV-2的专业知识，以及L博士实验室开发的细胞免疫学。Corey和D. Koelle与GenVec开发的最先进的腺病毒递送平台一起开发基于HSV-2、Ad 5的疫苗。