Recombinant Sendai Virus as Novel Paramyxovirus Vaccine

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最常见的原因。目前，还没有安全有效的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基因技术产生的新型Sendal病毒重组体(RSV)开发一种多价疫苗，将RSV和hPIV-3的关键抗原输送到儿童人群中。此外，基于这两种1型副流感病毒的相关性，SV主干将提供对hPIV-1的免疫力。 项目1的具体目标是我们实现这些目标的战略： 具体目的1：构建表达hPIV-3型和RSV(A、B型)包膜糖蛋白的RSV，并对其进行鉴定，获得一代重组鸡尾酒。 特异性目的2：比较表达RSV和hPIV-3靶糖蛋白的膜结合型和分泌型RSV的生长和靶基因表达。 具体目的3：制备和鉴定纯化的RSV和hPIV3包膜糖蛋白，作为ELISA监测抗体应答和增强RSV免疫应答的材料来源。 本项目与本申请中的另外两个项目高度相关，根据靶抗原表达方式不同的RSV构建体将由项目2的研究人员评估其免疫原性。因此，将在项目3中选择和制备用于评估非人类灵长类动物模型的安全性和保护性的配方。项目1、2和3的联合目标是将基于SV的呼吸道病毒疫苗推进到人体试验，以预防儿童严重的呼吸道病毒感染。

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.