New Nasal Spray Influenza Vaccine for Children

新型儿童鼻腔喷雾流感疫苗 项目摘要 尽管大力开展流感防治运动，流感仍是儿童面临的全球公共卫生问题 在许多国家接种疫苗。最近出现的新冠肺炎也可能使儿童流感复杂化 并使为幼儿接种流感疫苗变得更可取。流感疫苗必须 由于流行的流感病毒株的抗原性转变和漂移，每年重新配制。然而， 重新配制的季节性流感疫苗并不总是与流通的毒株相匹配，而且总是存在 禽流感病毒可能适应在人类中传播的威胁。此外，目前可用的 针对流感的抗病毒药物面临着进化耐药性和非特异性的双重挑战 效果。因此，迫切需要开发新的药物、疫苗和联合疗法。 预防流感病毒感染。 在这项拟议的研究中，我们假设一种普遍的预防和治疗性流感疫苗 可以通过产生一种自我减毒流感病毒(SAIV)来表达人工合成的 针对病毒和/或宿主基因表达的microRNAs(AmiRNAs)，这是病毒复制所必需的。按顺序 为了评估这一假设，我们为这项研究提出了以下三个具体目标： 具体目标1：评价候选预防和治疗性SAIV疫苗的效果 通过病毒基因靶向衰减。 特定目的2：评估宿主基因靶向产生的候选SAIV疫苗的有效性 衰减。 具体目标3：生产和评估额外的双重病毒和宿主因子-靶向预防和 治疗性SAIV疫苗。 我们在这项研究中开发的SAIV疫苗将在幼鼠身上进行广泛的研究 流感感染模型。我们预计，拟议的研究将确定一个新的和安全的普遍 流感疫苗和分子疗法，可进一步开发为治疗性疫苗，以预防 儿童未来的流感再感染。此外，这项研究计划将显著加强 位于埃尔帕索的德克萨斯理工大学健康科学中心的研究环境，并提供研究培训 分别为3名研究生、3名医学生和3名本科生提供机会， 在整个3年的绩效期间。

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.