Preclinical-Clinical Paramyxovirus Vaccine Development

临床前-临床副粘病毒疫苗开发

• 批准号: 6704020
• 负责人: ALLEN PORTNER
• 金额: $ 73.75万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6704020
• 关键词: clinical research; disease /disorder model; microorganism immunology; parainfluenza virus type 1; parainfluenza virus type 2; paramyxovirus vaccine; recombinant virus; respiratory syncytial virus; respiratory virus; vaccine development

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to obtain safe and effective vaccines for the prevention of the most common respiratory viruses of childhood, namely respiratory syncytial virus and human parainfluenza viruses, type 1 and 3. In spite of their epidemiologic importance, no vaccines exist for these pathogens. In this program it is proposed that the murine type 1 parainfluenza virus, Sendai virus, is an effective vaccine for its human cognate (human parainfluenza virus type 1; hPIV1). Based on our previous demonstration of SV-induced protection against hPIV1 in non-human primates and preliminary success in manipulating the cDNA of SV obtained through reverse genetics, we propose that SV can serve as an effective vaccine for hPIV1 and as a vaccine backbone for additional paramyxoviral antigens. The Paramyxovirus Vaccine Program at SJCRH integrates pre-clinical and clinical research and involves members of the Departments of Infectious Diseases, the Division of Virology and the Department of Immunology. This integrated, multidisciplinary approach is essential to ultimately determine the immunologic and virologic features that reliably predict paramyxovirus vaccine efficacy. The Program consists of 3 Projects: Project 1 - Recombinant Sendai virus as a novel paramyxovirus vaccine (PORTNER); Project 2 - Immune response and vaccine efficacy in a rodent model (HURWITZ); and Project 3 - Clinical and primate paramyxovirus vaccine evaluation (SLOBOD). The strengths of the Program are based in the strength of Sendai virus as a vaccine backbone and in the experience, skills and diversity of the assembled investigators working together towards a unified objective. Ultimately, this program will yield (1) a candidate respiratory virus vaccine; (2) reagents including a panel of 12 recombinant Sendai virus vaccines (differing according to target gene identity and mode of expression), monoclonal antibodies, purified recombinant proteins of hPIV-3 and RSV; and (3) information which can be applied to the study of paramyxovirus vaccine development, including T and B cell studies of durable immunity to these most common respiratory viruses. Taken together, this comprehensive program has a high likelihood of success, measured as the identification of protective and safe respiratory virus vaccines.

描述(申请人提供)：这项建议的长期目标是获得安全有效的疫苗，以预防儿童最常见的呼吸道病毒，即呼吸道合胞病毒和人类副流感病毒，1型和3型。尽管它们在流行病学上具有重要意义，但目前还没有针对这些病原体的疫苗。在这项计划中，提出了小鼠1型副流感病毒，仙台病毒，是一种有效的人类同源疫苗(人副流感病毒1型；hPIV1)。根据我们先前在非人类灵长类动物中证明了SV诱导的对hPIV1的保护作用，以及通过反向遗传学获得的SV的cDNA的初步成功，我们认为SV可以作为hPIV1的有效疫苗和额外的副粘病毒抗原的疫苗骨架。 SJCRH的副粘病毒疫苗计划整合了临床前和临床研究，并涉及传染病系、病毒学系和免疫学系的成员。这种综合的、多学科的方法对于最终确定可靠地预测副粘病毒疫苗效力的免疫学和病毒学特征至关重要。该计划由3个项目组成：项目1--重组仙台病毒作为一种新型副粘病毒疫苗(Portner)；项目2--啮齿动物模型中的免疫反应和疫苗效力(Hurwitz)；以及项目3--临床和灵长类副粘病毒疫苗评价(SLOBOD)。该计划的优势在于仙台病毒作为疫苗骨干的优势，以及聚集在一起的研究人员为实现统一目标而共同努力的经验、技能和多样性。最终，该计划将产生(1)候选呼吸道病毒疫苗；(2)包括12种重组仙台病毒疫苗(根据目标基因的一致性和表达方式而有所不同)、单克隆抗体、纯化的hPIV-3和RSV重组蛋白的试剂；以及(3)可用于副粘病毒疫苗开发研究的信息，包括对这些最常见的呼吸道病毒的T和B细胞持久免疫研究。总而言之，以识别保护性和安全的呼吸道病毒疫苗来衡量，这一综合计划成功的可能性很高。