New Nasal Spray Influenza Vaccine for Children

新型儿童鼻喷雾流感疫苗 项目摘要 流感仍然是一个全球性的公共卫生问题的儿童，尽管大力宣传流感 在许多国家接种疫苗。最近出现的COVID-19也可能使儿童流感复杂化 并使其更希望为幼儿接种流感疫苗。流感疫苗必须 由于流行性流感病毒株的抗原转移和漂移，每年重新配制。然而，在这方面， 重新配制的季节性流感疫苗并不总是与流行的毒株相匹配， 禽流感病毒可能适应在人类中传播的威胁。此外，目前可用 抗流感病毒药物正面临着进化的耐药性和非特异性副作用的双重挑战。 方面的影响.因此，迫切需要开发新的药物、疫苗和组合疗法 预防流感病毒感染。 在这项拟议的研究中，我们假设一种普遍预防和治疗流感的疫苗 可以通过创建表达人工合成的自减毒流感病毒（SAIV）来开发针对儿童的流感疫苗。 靶向病毒复制所必需的病毒和/或宿主基因表达的微小RNA（amiRNA）。为了 为了评估这一假设，我们提出了本研究的以下3个具体目标： 具体目的1：评价产生的候选预防性和治疗性SAIV疫苗的效力 通过病毒基因靶向衰减。 具体目的2：评估通过宿主基因靶向的SAIV疫苗产生的候选SAIV疫苗的有效性。 衰减 具体目标3：生产和评价额外的双重病毒和宿主因子靶向预防性和 SAIV疫苗。 我们在这项研究中开发的SAIV疫苗将在年轻小鼠中进行广泛研究 流感感染的模型。我们预计拟议的研究将确定一种新颖且安全的通用方法 流感疫苗和分子疗法，可进一步发展为治疗性疫苗， 未来流感再感染的儿童。此外，这项研究计划将大大加强 研究环境在得克萨斯理工大学健康科学中心在埃尔帕索，并提供研究培训 分别为3名研究生、3名医科学生和3名本科生提供机会， 在整个三年的业绩期间。

New Nasal Spray Influenza Vaccine for Children Project Summary Influenza is still a global public health problem for children despite a vigorous campaign for influenza vaccination in many countries. Recent emergence of the COVID-19 can also complicate influenza in children and make it more desirable to vaccinate young children against influenza. Influenza vaccines must be reformulated annually because of the antigenic shift and drift of circulating influenza viral strains. However, reformulated seasonal flu vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt for transmission in humans. Additionally, currently available antiviral drugs against influenza are facing the twin challenges of evolved drug resistance and nonspecific side effects. Therefore, there is an urgent need for developing novel drugs, vaccines, and combinatory therapies against influenza virus infection. In this proposed research, we hypothesize that a universally prophylactic and therapeutic influenza vaccine for children can be developed through creation of a self-attenuated influenza virus (SAIV) that expresses artificial microRNAs (amiRNAs) targeting viral and/or host gene expression that are essential for viral replication. In order to evaluate this hypothesis, we propose the following 3 specific aims for this research: Specific Aim 1: To evaluate the efficacy of a candidate prophylactic and therapeutic SAIV vaccine generated by viral gene-targeted attenuation. Specific Aim 2: To assess the efficacy of a candidate SAIV vaccine generated by host gene-targeted attenuation. Specific Aim 3: To produce and evaluate additional dual viral and host factor-targeted prophylactic and therapeutic SAIV vaccines. Our proposed SAIV vaccines developed in this research will be extensively investigated in young mouse model of influenza infection. We anticipate that the proposed research will identify a novel and safe universal influenza vaccine and molecular therapy that could be further developed as a therapeutic vaccine to prevent future influenza reinfection in children. Furthermore, this research program will significantly strengthen the research environment in Texas Tech University Health Sciences Center at El Paso, and provide research training opportunities for 3 graduate students, 3 medical students, and 3 undergraduate students, respectively, throughout the 3-year performance period.