Targeted Gene Expression from NL63 Vaccine Vectors

产品描述（由申请方提供）：安全有效的载体病毒疫苗在改善全球健康方面具有巨大潜力。在发展中国家，呼吸道和胃肠道感染是幼儿死亡的主要原因，需要能够在单剂量中安全递送多种疫苗抗原的疫苗平台。该提案的首要目标是开发人类冠状病毒NL63株作为异源疫苗载体，特别是用于发展中国家，这些国家难以获得用于改善人类健康的疫苗或知识产权。我们选择了NL63疫苗载体的开发和测试，因为它们将呼吸道病原体抗原递送到上呼吸道和下呼吸道内衬的适当粘膜上皮细胞，诱导强大的体液、粘膜和细胞免疫应答，基因组组织允许多种外源蛋白的同时和受调控的表达，并且已经开发了逆转和重组防止技术以使冠状病毒载体安全且复制缺陷。利用我们最近开发的人类冠状病毒株NL63的分子克隆，我们将使用计算机设计，合成基因组学和反向遗传学来设计安全的异源疫苗载体，以改善全球公共卫生。该提案的具体目标是建立候选载体，并为疫苗测试和开发开发建立动物模型基础设施。这些研究的影响可能很大，导致新的疫苗技术，以改善全球健康。 公共卫生相关性：在发展中国家，呼吸道和胃肠道感染是幼儿死亡的主要原因，需要能够在单剂量中安全递送多种疫苗抗原的疫苗平台。该提案的首要目标是开发人类冠状病毒NL63株作为异源疫苗载体，特别是用于发展中国家，这些国家难以获得用于改善人类健康的疫苗或知识产权。我们选择了NL63疫苗载体的开发和测试，因为它们将呼吸道病原体抗原递送到上呼吸道和下呼吸道内衬的适当粘膜上皮细胞，诱导强大的体液、粘膜和细胞免疫应答，基因组组织允许多种外源蛋白的同时和受调控的表达，并且已经开发了逆转和重组防止技术以使冠状病毒载体安全且复制缺陷。

DESCRIPTION (provided by applicant): Safe and effective vectored virus vaccines have great potential for improving global health. In the developing world, respiratory and gastrointestinal infections are major causes of death in young children and vaccine platforms are needed that can safely deliver multiple vaccine antigens in a single dose. The over-riding goal of this proposal is to develop the human coronavirus NL63 strain as a heterologous vaccine vector, especially for use in the developing world, which has poor access to vaccines or intellectual property dedicated toward improving human health. We have chosen the development and testing of NL63 vaccine vectors because they deliver respiratory pathogen antigens to the appropriate mucosal epithelial cells lining the upper and lower airways, induce robust humoral, mucosal and cellular immune responses, the genome organization allows for simultaneous and regulated expression of multiple foreign proteins, and reversion and recombination proof technologies have been developed to make coronavirus vectors safe and replication deficient. Using our recently developed molecular clone of the human coronavirus strain, NL63, we will use computer design, synthetic genomics and reverse genetics to engineer safe, heterologous vaccine vectors for the improvement of Global Public Health. The specific aims of this proposal are designed to build candidate vectors and to develop an animal model infrastructure for vaccine testing and development. The impact of these studies is potentially high, leading to new vaccine technologies for the improvement of global health. Public Health Relevance: In the developing world, respiratory and gastrointestinal infections are major causes of death in young children and vaccine platforms are needed that can safely deliver multiple vaccine antigens in a single dose. The over-riding goal of this proposal is to develop the human coronavirus NL63 strain as a heterologous vaccine vector, especially for use in the developing world, which has poor access to vaccines or intellectual property dedicated toward improving human health. We have chosen the development and testing of NL63 vaccine vectors because they deliver respiratory pathogen antigens to the appropriate mucosal epithelial cells lining the upper and lower airways, induce robust humoral, mucosal and cellular immune responses, the genome organization allows for simultaneous and regulated expression of multiple foreign proteins, and reversion and recombination proof technologies have been developed to make coronavirus vectors safe and replication deficient.