Development of a Vaccine to Protect Monkeys from Herpes B Virus Infection

开发一种疫苗来保护猴子免受 B 型疱疹病毒感染

• 批准号: 8048756
• 负责人: Anthony Griffiths
• 金额: $ 21.94万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-04 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8048756
• 关键词: 2 year old; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adult; Affect; Animal Model; Animals; Antibodies; Biology; Biomedical Research; Blood; Cells; Centers for Disease Control and Prevention (U.S.); Cercopithecine Herpesvirus 1; Chronic Disease; Communicable Diseases; Containment; Data; Detection; Development; Disease; Effectiveness; Excision; Exposure to; Foundations; Funding; Future; Gene Transduction Agent; Glycoproteins; Goals; Housing; Human; Immune response; Infection; Institution; Laboratories; Macaca; Measures; Methods; Modeling; Monkeys; Neurons; Oryctolagus cuniculus; Pathogenesis; Primates; Production; Protocols documentation; Recombinants; Research; Research Personnel; Retroviridae; Risk; Safety; Screening procedure; Severities; Simian Foamy Virus; Simplexvirus; Site; Specific Pathogen Frees; Time; Tissues; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Viral Antigens; Virus; Virus Diseases; Work; animal care; base; biodefense; cost; disorder prevention; efficacy testing; germ free condition; immunogenic; improved; innovation; latent infection; mortality; nonhuman primate; pathogen; programs; vaccine development; vaccine efficacy; vector; vector vaccine

DESCRIPTION (provided by applicant): Herpes B virus (BV) is a pathogen of macaques that is endemic in most macaque colonies. In macaques, BV infection is typically self-limiting. In contrast, BV can zoonotically infect humans and has a fatality rate of approximately 80%. Due to the severity of BV infections, the virus is classified by the CDC as a Risk Group 4 agent and may only be propagated in Biosafety Level 4 containment. Macaque monkeys are the most commonly used non-human primate in biomedical research. Their use is affected by the potential for BV infection to animal care staff and those handling macaque cells and tissues. The NIH funds several programs to generate macaque colonies free of BV. Unfortunately, the demand for BV-free animals far outstrips supply. BV-free animals are also expensive. The long-term goal of this project is to develop a BV vaccine that will protect macaque monkeys from BV infection. This will greatly improve the safety for animal care staff, increase the supply of SPF monkeys and decrease their cost. Toward this goal, we have generated a recombinant simian foamy virus (SFV) that expresses the immunogenic glycoprotein D (gD) from BV (BV gD/SFV). The objective of this application is to determine the ability of BV gD/SFV to induce a protective immune response in a model animal. To accomplish this objective, we will carry out the following two specific aims: 1) to determine the potency of BV gD/SFV vaccine in rabbits; 2) to determine the efficacy of the vaccine to protect rabbits from a lethal challenge of BV. The proposed project is significant because protecting monkeys from becoming infected with BV will greatly improve the ability to develop and maintain BV-free macaque colonies. The proposed study is innovative because of the focus on the development a vaccine that will protect monkeys from BV infection but not affect their use in future experimental protocols. Moreover, SFV-based vectors have been evaluated for use as gene therapy vectors but not as vaccine vectors. The successful completion of this project will provide data to support further studies to test the efficacy of the SFV- based vaccine in macaque monkeys. PUBLIC HEALTH RELEVANCE: Macaque monkeys are the most commonly used non human primate biomedical research. However, they are endemically infected with herpes B virus that causes a deadly infection in humans. A vaccine that protects monkeys from herpes B virus infection will greatly improve the safety of those working with these monkeys and their tissues, and thus improve the utility of these animals.

描述（由申请人提供）：疱疹病毒（BV）是猕猴的病原体，在大多数猕猴菌落中是地方性的。在猕猴中，BV感染通常是自限制的。相比之下，BV可以人死地感染人类，死亡率约为80％。由于BV感染的严重程度，该病毒被疾病预防控制中心分类为风险组4代理，并且只能在生物安全4级遏制中传播。猕猴是生物医学研究中最常用的非人类灵长类动物。它们的使用受到BV感染对动物护理人员以及处理猕猴细胞和组织的潜力的影响。 NIH资助了几个计划，以产生无BV的猕猴。不幸的是，对无BV动物的需求远远超过了供应。无BV的动物也很昂贵。该项目的长期目标是开发一种BV疫苗，该疫苗将保护猕猴免受BV感染。这将大大提高动物护理人员的安全性，增加SPF猴子的供应并降低其成本。为了实现这一目标，我们已经产生了一种重组邻氨酸泡沫病毒（SFV），该病毒表达了BV（BV GD/SFV）的免疫原性糖蛋白D（GD）。该应用的目的是确定BV GD/SFV在模型动物中诱导保护性免疫反应的能力。为了实现这一目标，我们将执行以下两个具体目标：1）确定兔子中BV GD/SFV疫苗的效力； 2）确定疫苗保护兔子免受BV致命挑战的疗效。拟议的项目具有重要意义，因为保护猴子免受BV感染将大大提高发展和维持无BV的猕猴菌落的能力。拟议的研究之所以创新，是因为专注于开发一种疫苗，该疫苗将保护猴子免受BV感染的影响，但不会影响其在未来的实验方案中的使用。此外，已经评估了基于SFV的载体作为基因疗法载体，但不是用作疫苗载体。该项目的成功完成将提供数据以支持进一步的研究，以测试基于SFV的疫苗在猕猴中的功效。 公共卫生相关性：猕猴是最常用的非人类灵长类动物生物医学研究。但是，它们在人体上感染了疱疹病毒，导致人类致命感染。一种保护猴子免受疱疹病毒感染的疫苗将大大提高与这些猴子及其组织一起工作的人的安全，从而改善这些动物的效用。