Transmission of CoV-2 and the Impact of Spike Protein Evolution

CoV-2 的传播和刺突蛋白进化的影响

• 批准号: 10587954
• 负责人: Adrianus CM Boon
• 金额: $ 58.16万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587954
• 关键词: 2019-nCoV; ACE2; Adenovirus Vector; Aerosols; Affect; Agonist; Animal Model; Animals; Antibodies; Bar Codes; Binding; COVID-19 susceptibility; COVID-19 vaccine; Cessation of life; Data; Dose; Epitopes; Event; Evolution; Future; Goals; Hamsters; Hour; Human; Immune; Immune response; Immunity; Immunization; Immunize; Immunoglobulin A; Immunoglobulin G; Incubated; Individual; Infection; Innate Immune Response; Innate Immune System; Interferons; Intramuscular; Kinetics; Location; Lower respiratory tract structure; Measures; Mesocricetus auratus; Modeling; Monoclonal Antibodies; Mucosal Immunity; Mucous Membrane; Mutation; Natural Immunity; Pan Genus; Persons; Process; Proteins; Publishing; Recombinant Interferon; Recombinants; Role; SARS-CoV-2 infection; SARS-CoV-2 transmission; SARS-CoV-2 variant; Severity of illness; Social Distance; Societies; Testing; Time; Upper Respiratory Infections; Upper respiratory tract; Vaccinated; Vaccines; Variant; Viral; Virion; Virus; Virus Diseases; adaptive immune response; adaptive immunity; emerging pathogen; in vivo; infection rate; influenzavirus; insight; neutralizing monoclonal antibodies; particle; pathogenic virus; prevent; protective effect; receptor binding; respiratory; respiratory virus; response; transmission process; vaccine delivery; variants of concern; viral transmission

PROJECT SUMMARY SARS-CoV-2 has led to unprecedented disruptions to society, killing more than 6 million people worldwide. It is a respiratory virus whose main mode of transmission is via respiratory droplets and aerosols. Social distancing and vaccines have greatly decreased the rate of infection and transmission. Despite these efforts, SARS-CoV- 2 transmission has continued. Moreover, different variants of concern, harboring signature mutations in the virus attachment Spike protein, have emerged. How these changes affect transmission of SARS-CoV-2 in naïve, infected and immunized individuals is not known. The transmission bottleneck is defined as the number of unique virus particles that establish an infection in the recipient host. This number is important as it determines the rate of evolution of the virus and the immune threshold required for protection from infection. This application will use barcoded or tagged SARS-CoV-2 to quantify how many virus particles establish an infection in the recipient host. We will use the Syrian hamster SARS-CoV-2 airborne transmission model to define how the innate and adaptive immune response in the donor and recipient host effect the number of unique transmission events. Using genetically modified hamsters that are deficient in their type I or III interferon response will be used to measure the role of innate immunity on SARS-CoV-2 transmission to the upper respiratory tract (URT) and subsequent dissemination of the virus to lower respiratory tract (LRT). Transmission and dissemination of SARS-CoV-2 will also be quantified in recipient animals that were previously infected with SARS-CoV-2, immunized with mucosal and systemic COVID-19 vaccines, or received neutralizing IgG and IgA antibodies. Finally, this application will measure the impact of immune escape on the transmission bottleneck in immune recipients. Fundamental insights into respiratory virus transmission and dissemination, transmission bottleneck and defining correlates of protection in the URT and LRT will inform future vaccine efforts against respiratory viruses.

项目摘要 SARS-CoV-2对社会造成了前所未有的破坏，在全世界造成600多万人死亡。是 一种主要通过呼吸道飞沫和气溶胶传播的呼吸道病毒。社交距离 疫苗大大降低了感染率和传播率。尽管有这些努力，SARS-CoV- 二是继续传输。此外，不同的变异的关注，窝藏签名突变的病毒 附着刺突蛋白，已经出现。这些变化如何影响SARS-CoV-2在初治患者中的传播， 感染和免疫的个体是未知的。传输瓶颈被定义为唯一的 在受体宿主中建立感染的病毒颗粒。这个数字很重要，因为它决定了 病毒的进化和保护免受感染所需的免疫阈值。该应用程序将使用 对SARS-CoV-2进行条形码化或标记，以量化多少病毒颗粒在受体宿主中建立感染。 我们将使用叙利亚仓鼠SARS-CoV-2空气传播模型来定义先天性和适应性 供体和受体宿主的免疫应答影响独特传播事件的数量。使用 将使用缺乏I型或III型干扰素反应的转基因仓鼠来测量 先天免疫在SARS-CoV-2传播至上呼吸道（URT）及随后的 病毒传播至下呼吸道（LRT）。SARS-CoV-2的传播和传播将 也可以在先前感染SARS-CoV-2的受体动物中定量， 和全身性COVID-19疫苗，或接受中和IgG和IgA抗体。最后，该应用程序将 测量免疫逃逸对免疫受者中传播瓶颈的影响。基本 深入了解呼吸道病毒的传播和传播、传播瓶颈和 URT和LRT中的保护将为未来针对呼吸道病毒的疫苗工作提供信息。