Pandemic Influenza Translational Research and novel universal countermeasure development

尽管进行了长期投资，流感仍然是一个重大的世界性问题。甲型流感病毒(IAV)是导致每年流行和偶尔大流行的重要人类病原体。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，但也对公共卫生具有重大意义。一种新的猪源甲型流感病毒在2009年成为大流行，导致41年来的第一次大流行。此外，每年的流行性流感病例也非常严重，导致美国每年高达4.9万人死亡。 我们继续人类挑战工作，开发新的挑战模型，并继续使用我们之前开发的H1N1和H3N1模型。SARS-CoV-2大流行限制了我们在2020至2022年间使用这些模型的工作，但我们现在正在大流行后时期再次向前迈进。我们已经完成了对一项评估粘膜免疫的挑战性研究的分析，这项研究将于今年晚些时候发表。我们将在下一财年的第一季度启动一项针对新型低致病性H10N7亚型禽流感病毒的挑战研究，我们正在组织合作，在下一财年研究我们的2013瑞士H3N2挑战病毒在人类身上的应用。我们继续生产和维护GMP制造的有用的挑战病毒，包括大流行前的H1N1病毒和B型流感病毒。 在过去的一年里，我们完成了与DMID的合作，我们的H1N1挑战病毒和挑战方案被用于VTEU系统的挑战研究。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，导致其他合作和更大的项目。 我们继续我们的血清学研究，包括我们对参与挑战研究后的个人的长期研究。我们还完成了一项评估流感疫苗接种后儿童黏膜和系统免疫的临床研究，我们预计将在来年发表这项研究，并将继续招募一项关于接种COVID和流感疫苗后成人的纵向研究，以评估他们的黏膜和系统反应，以及两者之间的相互作用。 除了这些临床研究外，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。

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.