New Nasal Spray Influenza Vaccine for Children (Research Supplement for Post Baccalaureate Diversity Candidate)

儿童新型鼻喷雾流感疫苗（学士学位后多样性候选人的研究补充）

• 批准号: 10838135
• 负责人: MINGTAO ZENG
• 金额: $ 14.58万
• 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/10838135
• 关键词: Antiviral Agents; Attenuated; Avian Influenza A Virus; COVID-19; Child; Country; Drug resistance; Environment; Funding; Future; Gene Expression; Gene Targeting; Health Sciences; Human; Infection; Influenza; Influenza Therapeutic; Influenza vaccination; Integration Host Factors; Medical Students; MicroRNAs; Molecular; Nose; Performance; Postbaccalaureate; Preventive vaccine; Public Health; Research; Research Training; Texas; Therapeutic; Twin Multiple Birth; Universities; Vaccinated; Vaccines; Viral; Viral Genes; Virulent; Virus; Virus Replication; attenuation; efficacy evaluation; graduate student; influenza infection; influenza virus strain; influenza virus vaccine; influenzavirus; mouse model; novel; novel therapeutics; novel vaccines; prevent; programs; prophylactic; public health relevance; seasonal influenza; side effect; therapeutic vaccine; training opportunity; transmission process; undergraduate student; universal influenza vaccine; vaccine development

New Nasal Spray Influenza Vaccine for Children (Research Supplement for R15HD109732) Project Summary/Abstract: 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 graduate students, medical students, and undergraduate students, throughout the 3-year performance period. This research supplement fund will support the diversity candidate, Ms. Alejandra Munoz, for 2 year post-baccalaureate research training through this research program.

新型儿童鼻喷雾流感疫苗 （R15HD109732 的研究补充） 项目摘要/摘要： 尽管开展了强有力的流感防治运动，但流感仍然是儿童的全球公共卫生问题 许多国家都接种了疫苗。最近出现的 COVID-19 也可能使儿童流感复杂化 并让幼儿接种流感疫苗变得更加可取。流感疫苗必须 由于流行的流感病毒株的抗原转变和漂移，每年都会重新配制。然而， 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，并且始终存在 禽流感病毒可能适应在人类中传播的威胁。另外，目前可用 流感抗病毒药物面临耐药性和非特异性的双重挑战 副作用。因此，迫切需要开发新的药物、疫苗和组合药物 针对流感病毒感染的疗法。 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 可以通过创建自减毒流感病毒（SAIV）来开发儿童疫苗 表达针对病毒和/或宿主基因表达的人工 microRNA (amiRNA)，这对于病毒和/或宿主基因表达至关重要 病毒复制。为了评估这一假设，我们提出本研究的以下 3 个具体目标： 具体目标 1：评估候选预防性和治疗性 SAIV 疫苗的功效 由病毒基因靶向减毒产生。 具体目标 2：评估通过宿主基因靶向产生的候选 SAIV 疫苗的功效 衰减。 具体目标 3：生产和评估额外的双病毒和宿主因子靶向预防和治疗药物 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研究 流感感染模型。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以进一步开发为治疗性疫苗，以预防 未来儿童再次感染流感。此外，该研究计划将显着加强 德克萨斯理工大学埃尔帕索健康科学中心的研究环境，并提供研究 为研究生、医学生和本科生提供培训机会 3年业绩期。 该研究补充基金将为多元化候选人 Alejandra Munoz 女士提供为期 2 年的支持 通过该研究计划进行学士学位后研究培训。