Role of preexisting immunity on airborne transmission of influenza viruses

预先存在的免疫力对流感病毒空气传播的作用

• 批准号: 10765989
• 负责人: Seema S. Lakdawala
• 金额: $ 63.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10765989
• 关键词: Age; Air; Animal Model; Animals; Antibodies; Attenuated; Cellular Immunity; Data; Ensure; Environment; Epidemic; Epidemiology; Evolution; Exposure to; Ferrets; Future; Goals; Human; Immune; Immune response; Immunity; Immunologic Factors; Immunologics; Immunology; Individual; Infection; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Letters; Longevity; Medicine; Modeling; Mucosal Immune Responses; Nature; Pathogenesis; Peripheral; Population; Predisposition; Public Health; Publishing; Regimen; Research; Role; Seasons; Shapes; T-Lymphocyte; Tissues; Vaccinated; Vaccination; Vaccines; Viral; Viral Proteins; Virus; Virus Diseases; Work; animal model development; cross reactivity; fitness; flu transmission; influenza virus strain; influenzavirus; neutralizing antibody; new pandemic; novel; pandemic disease; pandemic virus; pathogen; pressure; prevent; respiratory virus; seasonal influenza; success; transmission process; universal vaccine; vaccine effectiveness; vaccine efficacy; vaccine platform; vaccine strategy; viral transmission; virology

SUMMARY: Role of Pre-existing Immunity on Airborne Transmission of Influenza A Viruses Influenza viruses pose a major public health threat through both seasonal epidemics and sporadic pandemics. The epidemiological success of influenza viruses relies on its ability to spread efficiently through the air and navigate three distinct spaces: 1) the donor, 2) the environment and 3) the recipient (Lakdawala and Subbarao Nature Medicine 2012). The first infection with influenza viruses leaves a long-lasting immunity, which can be evaded by the virus through antigenic drift and shift. Our published data using the ferret model shows that pre-existing immunity from the 2009 H1N1 pandemic virus infection protects recipient animals from airborne transmission of a seasonal H3N2 influenza virus (Le Sage et al PLoS Pathogens 2021). We hypothesize that pre-existing immunity can influence susceptibility to circulating influenza strains independent of neutralizing antibody. To understand the role of pre-existing immunity in protection against airborne transmission, Aim 1 will identify immunological and viral factors underlying susceptibility to airborne transmission. Each influenza season, population-wide immunity triggers viral antigenic evolution, Aim 2 will determine the impact of antigenic drift on the susceptibility to influenza virus transmission. Aim 3 will examine the impact of different vaccine platforms on susceptibility to drifted influenza virus strains. This proposal will provide a better understanding of the immune protection needed to dampen influenza virus transmission and inform effective universal vaccine strategies.

摘要：预先存在的免疫力对机载的作用 甲型流感病毒的传播 流感病毒通过季节性流行和零星流行对公共健康构成重大威胁。 流行病。流感病毒在流行病学上的成功取决于其传播能力 有效地在空中飞行并导航三个不同的空间：1）捐赠者，2）环境 3) 接受者（Lakdawala 和 Subbarao Nature Medicine 2012）。首次感染 流感病毒会留下持久的免疫力，病毒可以通过以下方式逃避这种免疫力： 抗原漂移和转移。我们使用雪貂模型发布的数据表明，预先存在的 对 2009 年 H1N1 大流行病毒感染的免疫力可保护受体动物免受空气传播的影响 季节性 H3N2 流感病毒的传播（Le Sa​​ge 等 PLoS Pathogens 2021）。我们 假设预先存在的免疫力会影响对流行性流感的易感性 菌株独立于中和抗体。了解预先存在的免疫力在 防止空气传播，目标 1 将识别免疫和病毒因素 对空气传播的潜在易感性。每个流感季节，全人群 免疫触发病毒抗原进化，目标2将确定抗原漂移对病毒的影响 流感病毒传播的易感性。目标 3 将考察不同因素的影响 对漂移的流感病毒株易感性的疫苗平台。该提案将提供一个 更好地了解抑制流感病毒传播所需的免疫保护 并为有效的通用疫苗策略提供信息。