Susceptibility and Protective Immunity to Noroviruses

对诺如病毒的易感性和保护性免疫

• 批准号: 7159338
• 负责人: Ralph S Baric
• 金额: $ 37.66万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2009-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159338
• 关键词: Alleles; Alphavirus; Bioterrorism; Caliciviridae; Capsid; Categories; Centers for Disease Control and Prevention (U.S.); Child; Development; Diarrhea; Dose; Economics; Edible Vaccines; Epidemic; Gastroenteritis; Genes; Goals; Human; Immune; Immunity; Infectious Diseases Research; Integration Host Factors; Modeling; Molecular; Molecular Biology; Mucosal Immune Responses; National Institute of Allergy and Infectious Disease; Norovirus; Outcome; Pathogenicity; Predisposition; Replicon; Standards of Weights and Measures; Testing; United States National Institutes of Health; Vaccines; Venezuelan Equine Encephalitis Virus; Virus; Virus Diseases; Virus-like particle; base; biodefense; insight; particle; pathogen; recombinant virus; response; therapeutic vaccine; vaccine development; vector vaccine; virus pathogenesis

Norwalk-like viruses (NLV), a genus within the Caliciviridae, are the major cause of epidemic gastroenteritis in the US and a significant cause of severe diarrhea in young children[16]. Based on their low infectious dose, high transmissibility and economic impact, NLVs have been classified as Bioterrorism Category B Priority Pathogens by the U.S. Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases (http://www.niaid.nih.gov/dmid/bioterrorism/). The proposal is responsive to NIH NOT-AI-02-023, Biodefense and Emerging Infectious Disease Research Opportunities (http:/Iwww.niaid.nih.gov/dmidlbioterrorismlrfalplat.htm). The long-term goals of this proposal are to elucidate the molecular mechanisms governing human susceptibility to NLV infection. In this capacity, we will use human challenge models to test various hypotheses that specific human susceptibility alleles and acquired immune factors determine NLV infection outcomes and pathogenicity. It is anticipated that the identification of host factors and responses that influence NLV pathogenesis will reveal fundamental insights into the molecular biology of these viruses, simultaneously allowing for the development of NLV vaccine and therapeutic strategies. A second goal is to develop NLV vaccines using alphaviruses as heterologous vaccine vectors. Venezuelan equine encephalitis virus (VEE)-based vaccines elicit high levels of mucosal and systemic immunity against NLVs [2, 3, 17-19]. We will test various hypotheses that VEE replicon particles (VRPs) encoding different genogroup I and II (GI and GII) NLV capsid genes elicit strong systemic, cellular and mucosal immune responses against homologous and heterologous NLVs and are superior to the current standards for NLV vaccine development (NLV recombinant virus-like particles (VLPs) and edible vaccines).

诺瓦克样病毒(NLV)是杯状病毒科的一个属，是引起流行性胃肠炎的主要原因 在美国，这是导致幼儿严重腹泻的重要原因[16]。基于他们的低传染性 NLV具有高剂量、高传播性和经济影响，已被列为生物恐怖主义B类 美国疾病控制和预防中心和国家疾病控制和预防研究所的优先病原体 变态反应和传染病(http://www.niaid.nih.gov/dmid/bioterrorism/).该提案是对以下方面的回应 NIH NOT-AI-02-023，生物防御和新发传染病研究机遇 (http:/Iwww.niaid.nih.gov/dmidlbioterrorismlrfalplat.htm).这项提议的长期目标是澄清 人类对NLV感染易感性的分子机制。在这个职位上，我们将使用 人类挑战模型，以测试各种假设，即特定的人类易感基因和获得性 免疫因素决定NLV感染结果和致病性。预计这一身份证明 影响NLV发病的宿主因素和反应将揭示对NLV致病的基本见解 这些病毒的分子生物学，同时允许开发NLV疫苗和 治疗策略。第二个目标是开发使用甲型病毒作为异源的NLV疫苗 疫苗载体。委内瑞拉马脑炎病毒(VEE)疫苗诱导高水平粘膜 和对NLV的系统免疫[2，3，17-19]。我们将测试VEE复制图标的各种假设 编码不同基因组I和II(GI和GII)NLV衣壳基因的颗粒(VRP)可诱导强烈的系统性， 针对同种和异种NLV的细胞和粘膜免疫反应优于 目前NLV疫苗开发的标准(NLV重组病毒样颗粒(VLP)和可食性 疫苗)。