Pandemic Influenza Translational Research and novel universal countermeasure development

大流行性流感转化研究和新型通用对策开发

• 批准号: 10927867
• 负责人: Matthew Memoli
• 金额: $ 534.36万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10927867
• 关键词: 1918 influenza pandemic; Adult; Avian Influenza A Virus; COVID-19 pandemic; Cessation of life; Child; Clinical Protocols; Clinical Research; Collaborations; Development; Enrollment; Epidemic; Family suidae; Goals; Human; Human Volunteers; Immunity; Individual; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza B Virus; Influenza vaccination; Investments; Longitudinal Studies; Modeling; Morbidity - disease rate; Mucosal Immunity; Mucous Membrane; National Institute of Allergy and Infectious Disease; Natural History; Pathogenesis; Persons; Process; Protocols documentation; Public Health; Publishing; Serology; Switzerland; System; Therapeutic; Translational Research; Virus; Virus Diseases; Work; diagnostic tool; human pathogen; influenza epidemic; influenza infection; influenzavirus; manufacture; mortality; novel; novel therapeutics; novel vaccines; pandemic disease; pandemic influenza; patient population; post-COVID-19; post-pandemic; pre-pandemic; previous pandemic; programs; response; seasonal influenza; vaccine strategy; volunteer

Despite long-term investment, influenza continues to be a significant worldwide problem. Influenza A viruses (IAV) are significant human pathogens causing yearly epidemics and occasional pandemics. Past pandemics have resulted in significant morbidity and mortality. The 1918 influenza pandemic was thought to have resulted in the death of at least 675,000 people in the U.S. and 40 million people worldwide. Pandemics in 1957 and 1968, while less severe, were also of major public health importance. A novel influenza A virus of swine origin became pandemic in 2009, causing the first pandemic in 41 years. In addition, annual epidemic influenza cases are also very significant resulting in up to 49,000 deaths in the U.S. annually. We continue our human challenge work both developing novel challenge models and continuing to utilize our previously developed models fo H1N1 and H3N2. The SARS-CoV-2 pandemic limited our work with these models during 2020 and 2022 but we are now moving forward again in this post-pandemic period. We have completed analysis of a challenge study performed to evaluate mucosal immunity, which we will publish later this year. We are set to start a challenge study with a novel low pathogenesis avian influenza virus of subtype H10N7 in the first quarter of the next fiscal year, and we are in the process of putting together collaborations to study our 2013 Switzerland H3N2 challenge virus in humans in this next fiscal year as well. We continue to produce and maintain GMP manufactured useful challenge viruses including a pre-pandemic H1N1 and an influenza-B viruses. This past year we completed our collaboration with DMID where our H1N1 challenge virus and challenge protocol was used in a challenge study in the VTEU system. This has been instrumental in expanding challenge capacity in the U.S. and moving the influenza challenge field forward leading to other collaborations and larger programs. We continue with our serological studies including our long term study of individuals post participation in a challenge study. We also have completed a clinical study evaluating mucosal and systemic immunity in children after influenza vaccination that we expect to publish in the coming year as well as are continuing to enroll a longitudinal study of adults post COVID and Influenza vaccination to evaluate their mucosal and systemic responses, as well as the interactions between the two. In addition to these clinical studies we continued our collaborations with Stanford, FDA, and within NIAID to further study human influenza infection and how it relates to other viral infections.

尽管进行了长期投资，但流感仍然是一个重大的世界性问题。甲型流感病毒（Influenza A virus，IAV）是人类重要的病原体，每年都会引起流行病，偶尔也会引起大流行。过去的大流行导致了严重的发病率和死亡率。1918年的流感大流行被认为导致美国至少67.5万人死亡，全球4000万人死亡。1957年和1968年的大流行虽然不那么严重，但也具有重大的公共卫生意义。2009年，一种新型猪源甲型流感病毒大流行，导致41年来首次大流行。此外，每年流行性流感病例也非常显著，导致美国每年多达49，000人死亡。 我们继续我们的人类挑战工作，开发新的挑战模型，并继续利用我们以前开发的H1N1和H3N2模型。 在2020年和2022年，SARS-CoV-2大流行限制了我们使用这些模型的工作，但我们现在在大流行后的时期再次向前迈进。 我们已经完成了一项评估粘膜免疫的攻毒研究的分析，我们将在今年晚些时候发表。 我们将在下一财年的第一季度开始一项新的低致病性H10N7亚型禽流感病毒的挑战研究，我们也正在合作研究2013年瑞士H3N2人类挑战病毒。 我们继续生产和维护GMP生产的有用的挑战病毒，包括大流行前的H1N1和流感病毒B。 在过去的一年里，我们完成了与DMID的合作，在VTEU系统的挑战研究中使用了我们的H1N1挑战病毒和挑战方案。 这有助于扩大美国的挑战能力，并推动流感挑战领域向前发展，从而导致其他合作和更大的项目。 我们继续进行血清学研究，包括对参与攻毒研究后的个体的长期研究。 我们还完成了一项临床研究，评估了流感疫苗接种后儿童的粘膜和全身免疫力，我们预计将于明年发表，并将继续招募成年人接种COVID和流感疫苗后的纵向研究，以评估他们的粘膜和全身反应，以及两者之间的相互作用。 除了这些临床研究，我们继续与斯坦福大学、FDA和NIAID合作，进一步研究人类流感感染及其与其他病毒感染的关系。

项目成果

Pandemic research in the ICU: always be prepared.

重症监护室的流行病研究：时刻做好准备。

• DOI: 10.1097/ccm.0b013e31827c0605
• 发表时间: 2013
• 期刊: Critical care medicine
• 影响因子: 8.8
• 作者: Memoli,MatthewJames

In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient.

• DOI: 10.1016/j.virol.2012.02.018
• 发表时间: 2012-06-20
• 期刊: Virology
• 影响因子: 3.7
• 作者: Memoli MJ;Bristol T;Proudfoot KE;Davis AS;Dunham EJ;Taubenberger JK
• 通讯作者: Taubenberger JK

Efficacy Analysis in Healthy-Volunteer Influenza Challenge Trials: Intention To Treat.

健康志愿者流感挑战试验的功效分析：治疗意向。

• DOI: 10.1128/aac.02018-17
• 发表时间: 2018
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Hunsberger,Sally;Memoli,MatthewJ
• 通讯作者: Memoli,MatthewJ

Best to Exclude but Pay.

最好排除但付费。

• DOI: 10.1080/15265161.2018.1431707
• 发表时间: 2018
• 期刊: The American journal of bioethics : AJOB
• 作者: Danis,Marion;Doernberg,Sam;Memoli,Matthew;Millum,Joseph
• 通讯作者: Millum,Joseph

Reply to Bernstein, Atmar, and Hoft.

回复伯恩斯坦、阿特马尔和霍夫特。

• DOI: 10.1093/cid/ciaa279
• 发表时间: 2020
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Han,Alison;Taubenberger,JefferyK;Memoli,MatthewJ
• 通讯作者: Memoli,MatthewJ