New Nasal Spray Influenza Vaccine for Children

新型儿童鼻喷雾流感疫苗

• 批准号: 10653579
• 负责人: MINGTAO ZENG
• 金额: $ 48万
• 依托单位: TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER AT EL PASO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-10 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653579
• 关键词: Adult; Animals; Antiviral Agents; Attenuated; Avian Influenza A Virus; Birds; COVID-19; Cells; Characteristics; Child; Country; Dose; Drug resistance; Effectiveness; Engineering; Environment; Federal Government; FluMist; Future; Gene Expression; Gene Targeting; Genes; Goals; Health Sciences; Hispanic-serving Institution; Human; Immune; Immune response; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza Therapeutic; Influenza vaccination; Integration Host Factors; Licensing; Mammalian Cell; Medical Students; MicroRNAs; Modeling; Molecular; Mus; Mutation; Nose; Nucleoproteins; Performance; Pharmaceutical Preparations; Phosphotransferases; Prevention; Preventive vaccine; Prophylactic treatment; Public Health; RNA Interference; Recombinants; Research; Research Training; Site; System; Technology; Texas; Therapeutic; Therapeutic Effect; Treatment Efficacy; Twin Multiple Birth; Universities; Vaccinated; Vaccination; Vaccines; Viral; Viral Genes; Virulent; Virus; Virus Replication; anti-influenza; attenuation; chicken egg; efficacy evaluation; genome-wide; graduate student; influenza infection; influenza virus strain; influenza virus vaccine; influenzavirus; mouse model; novel; novel therapeutics; novel vaccines; pathogenic virus; prevent; programs; prophylactic; prototype; public health relevance; risk minimization; seasonal influenza; side effect; therapeutic vaccine; training opportunity; transmission process; undergraduate student; universal influenza vaccine; vaccine access; vaccine development

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.

新的鼻鼻喷雾流感疫苗 项目摘要 尽管流感激烈的运动，流感仍然是儿童的全球公共卫生问题 许多国家的疫苗接种。 COVID-19的最新出现也可能使儿童流感复杂化 并使接种幼儿对流感疫苗接种疫苗更为理想。流感疫苗必须是 每年重新构建，因为循环流感病毒菌株的抗原转移和漂移。然而， 重新制定的季节性流感疫苗并不总是与循环菌株相匹配，而且有永远存在的疫苗 禽流感病毒可能适应人类传播的威胁。此外，目前可用 针对流感的抗病毒药物正面临进化的耐药性和非特异性方面的双重挑战 效果。因此，迫切需要开发新型药物，疫苗和联合性疗法 抗流感病毒感染。 在这项拟议的研究中，我们假设一种普遍的预防性和治疗性流感疫苗 可以通过形成自我衰减的流感病毒（SAIV）来开发儿童 针对病毒复制至关重要的病毒和/或宿主基因表达的microRNA（amiRNA）。为了 为了评估这一假设，我们提出了以下3个针对这项研究的特定目标： 特定目的1：评估产生的预防和治疗性SAIV疫苗的疗效 通过病毒基因靶向衰减。 特定目的2：评估宿主基因靶向候选的SAIV疫苗的功效 衰减。 特定目的3：生产和评估其他双重病毒和宿主因子的预防性和 治疗性SAIV疫苗。 我们在这项研究中开发的拟议的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个新颖且安全的普遍性 流感疫苗和分子疗法可以作为治疗疫苗进一步开发 未来的流感儿童感染。此外，该研究计划将大大加强 德克萨斯理工大学的研究环境El Paso，并提供研究培训 分别为3名研究生，3名医学生和3名本科生的机会 在整个三年期间。