Recombinant Sendai Virus as Novel Paramyxovirus Vaccine

重组仙台病毒作为新型副粘病毒疫苗

• 批准号: 7433803
• 负责人: ALLEN PORTNER
• 金额: $ 26.83万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7433803
• 关键词: Acute; Antibody Formation; Antigen Targeting; Antigens; Binding; Child; Childhood; Drug Formulations; Enzyme-Linked Immunosorbent Assay; Evaluation; Gene Expression; Generations; Genetic Techniques; Glycoproteins; Growth; Human; Human Parainfluenza Virus 1; Human Parainfluenza Virus 3; Human respiratory syncytial virus; Immunity; Infant; Lung diseases; Membrane; Modeling; Monitor; Para-Influenza Virus Type 1; Population; Prevention; Recombinants; Research Personnel; Respiratory syncytial virus; Safety; Sendai virus; Source; Vaccines; Vertebral column; Viral; base; immunogenicity; nonhuman primate; novel; paramyxovirus vaccine; pathogen; positional cloning; programs; recombinant virus; respiratory infection virus; respiratory virus; response

Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIV) types 1 and 3 are the most common causes of acute viral respiratory disease in infants and young children. Currently, no safe and effective RSV or PIV vaccine has been developed for the prevention of these pathogens. The objective of the multi-project program is to develop a multivalent vaccine using novel Sendal virus recombinants (rSV), generated by reverse genetic techniques, to deliver critical antigens of RSV and hPIV-3 to the pediatric population. In addition, the SV backbone will provide immunity against hPIV-1 based on relatedness of these two type 1 parainfluenza viruses. The Specific Aims of Project 1 descdbe our strategy to meet these objectives: Specific Aim 1: To construct and characterize a set of rSV expressing the envelope glycoproteins of hPIV-3 and RSV (types A and B), yielding a cocktail of first generation recombinants. Specific Aim 2: To compare the growth and target gene expression of rSV expressing membrane-bound versus secreted forms of the target glycoproteins of RSV and hPIV-3. Specific Aim 3: To prepare and characterize purified RSV and hPIV3 envelope glycoproteins, as a source of material for ELISA monitoring of antibody response and for possible boosting of rSV primed responses. This Project is highly related to the other two Projects in this application, rSV constructs, which differ according to the mode of the target antigen expression will be evaluated for immunogenicity by Project 2 investigators. Superior rSV will thus be selected and prepared in a formulation for the evaluation of safety and protection in a non-human primate model in Project 3. The combined Aims of Projects 1, 2 and 3 are intended to advance a SV-based respiratory virus vaccine to human trial for the prevention of serious respiratory virus infections in children.

呼吸道合胞病毒（RSV）和人类副流感病毒（hPIV） 1型和3型是婴幼儿急性病毒性呼吸道疾病的最常见原因。目前，还没有开发出安全有效的RSV或PIV疫苗来预防这些病原体。该多项目计划的目标是利用反向遗传技术产生的新型森达尔病毒重组（rSV）开发一种多价疫苗，将rSV和hPIV-3的关键抗原传递给儿科人群。此外，基于这两种1型副流感病毒的亲缘关系，SV主干将提供对hPIV-1的免疫力。