Innate Control of Adaptive Immunity to SARS-CoV-2

对 SARS-CoV-2 的适应性免疫的先天控制

• 批准号: 10284699
• 负责人: Benjamin Goldman-Israelow
• 金额: $ 19.37万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10284699
• 关键词: 2019-nCoV; Acute; Address; Adjuvant; Advisory Committees; Antibodies; Antibody Formation; Antibody titer measurement; Antiviral Agents; B-Lymphocytes; COVID-19; Cells; Cessation of life; Communicable Diseases; Complex; Coronavirus; Cytokine Signaling; DNA; Data; Dendritic Cells; Development; Doctor of Medicine; Doctor of Philosophy; Etiology; Fellowship Program; Future; Genotype; Goals; Grooming; Hospitals; Humoral Immunities; IFNAR1 gene; Immune; Immune response; Immune signaling; Immunity; Immunobiology; Immunoglobulin A; Immunologics; Immunology; Infection; Influenza A Virus, H1N1 Subtype; Influenza A virus; Infrastructure; Innate Immune Response; Innate Immune System; Interferon Type I; Interferons; Internal Medicine; Journals; Kinetics; Knowledge; Laboratories; Lead; Location; Medicine; Mentors; Mentorship; Methods; Molecular Virology; Morbidity - disease rate; Mucosal Immunity; Mucous Membrane; Mus; Natural Immunity; Pathology; Pathway interactions; Pattern recognition receptor; Physicians; Principal Investigator; Production; Program Development; Publishing; RNA; Receptor Signaling; Records; Research; Research Personnel; Research Training; Residencies; Resources; Role; SARS-CoV-2 immunity; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; Science; Scientist; Shapes; Signal Transduction; Stimulator of Interferon Genes; T-Lymphocyte; Training; Training Programs; Vaccination; Vaccines; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Wild Type Mouse; Work; Writing; ZIKA; adaptive immune response; adaptive immunity; base; career; career development; cell type; coronavirus disease; coronavirus vaccine; design; human coronavirus; immune activation; immunopathology; improved; inhibiting antibody; medical schools; mortality; mouse model; mucosal vaccination; mucosal vaccine; pandemic disease; pandemic influenza; pathogen; receptor; respiratory virus; response; sensor; tool; translational scientist; vaccine development; vaccine trial

Project Summary/Abstract To date, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) has caused over 32 million cases of coronavirus disease (COVID-19), with ~1 million associated deaths. Multiple vaccine trials have begun in an effort to stop this pandemic, yet the correlates of viral clearance and immune protection from SARS-CoV-2 remain unknown. In fact, there are no licensed vaccines to any human coronavirus, as we have not yet discovered the immunologic correlates of a successful coronavirus vaccine. In his brief tenure in the Iwasaki lab, Dr. Goldman-Israelow has already developed a highly adaptable mouse model of SARS-CoV-2 infection that can be applied to mice of any genotype. He published this work as co-first author in the Journal of Experimental Medicine. He also showed that innate immune activation drives acute pathology. However, the extent to which innate immune signals drive adaptive immunity remains to be explored. This proposal will address how: (1) type I interferon signaling and (2) cGAS signaling control antibody development to SARS- CoV-2. This work is critical for characterizing the fundamental rules that govern adaptive immunity to SARS- CoV-2, which will promote the development of highly effective vaccines. This proposal describes a rigorous five-year career development training program for Benjamin Goldman- Israelow, M.D., Ph.D., with the goal of preparing him for an independent research career as an academic physician-scientist. The principal investigator is a physician scientist who completed his M.D. and Ph.D. training in Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, where he studied molecular virology. Dr. Goldman-Israelow continued his training by joining the Physician Scientist Research Pathway at Yale New Haven Hospital, a combined residency and fellowship program, and is currently an infectious diseases fellow. He has embarked on an intensive training program to broaden his expertise in viral immunology under the mentorship of Dr. Akiko Iwasaki, a pioneer and world leader in deciphering the complex interplay among viruses, innate immune recognition, and adaptive immunity. Dr. Iwasaki is not only a world- class scientist, but also a world-class mentor with a very productive track record of mentoring physician- scientists. In addition to the intellectual grooming and practical laboratory-based training that Dr. Goldman- Israelow will continue to receive in Dr. Iwasaki’s lab, he has developed a training program built on high-yield didactic coursework. He has also carefully crafted an advisory committee comprising translational scientists with a broad range of scientific expertise relevant to this proposal and impressive records of mentorship. Yale School of Medicine, along with its Departments of Internal Medicine and Immunobiology, will provide the resources, support, and infrastructure to assist Dr. Goldman-Israelow in achieving the aims described in this proposal and his long-term goal of developing into an independent physician-scientist studying the rules that govern antibody development to both viral infection and vaccination.

项目摘要/摘要 迄今为止，严重的急性呼吸综合症冠状病毒2（SARS-COV-2）已导致超过3200万 冠状病毒病例（Covid-19），约有100万相关死亡。多次疫苗试验具有 始于阻止这种大流行的努力，但病毒清除和免疫保护的相关性 SARS-COV-2仍然未知。实际上，我们拥有的任何人类冠状病毒都没有许可的疫苗 尚未发现成功的冠状病毒疫苗的免疫学相关性。在他短暂的任期 Iwasaki Lab，Goldman-Israelow博士已经开发了一种高度适应的SARS-COV-2的鼠标模型 可应用于任何基因型的小鼠的感染。他在《杂志》杂志上发表了这项工作 实验医学。他还表明，先天免疫激活驱动了急性病理学。但是， 先天免疫信号驱动适应性免疫疾病的程度仍有待探索。该提议将 地址：（1）I型干扰素信号传导和（2）CGAS信号控制对SARS-的抗体发展 COV-2。这项工作对于表征针对SARS的适应性免疫学的基本规则至关重要。 COV-2，它将促进高效疫苗的开发。 该提案描述了本杰明·高盛（Benjamin Goldman）的一项严格的五年职业发展培训计划 医学博士Israellow博士，目的是为他作为学术生涯做好准备 医师科学家。首席研究人员是一位物理科学家，他完成了医学博士学位和博士学位。 西奈山的伊坎医学院的生物医学科学培训，在那里他研究了分子 病毒学。高盛（Goldman-Israelow）博士继续接受培训 耶鲁·纽黑文医院（Yale New Haven Hospital）是一项综合住宅和奖学金计划，目前是一个传染性的 疾病研究员。他开始了一项强化培训计划，以扩大他在病毒方面的专业知识 免疫学是在阿基科·伊瓦萨基（Akiko Iwasaki）的心态下，他是综合体的开拓者和世界领导者 病毒，先天免疫认知和适应性免疫学之间的相互作用。伊瓦萨基博士不仅是一个世界 - 班级科学家，也是世界一流的心理 科学家。除了高盛博士 Israellow将继续在Iwasaki博士的实验室中获得 教学课程。他还精心制作了一个咨询委员会，完成了翻译科学家 具有与该提案有关的广泛科学专业知识和令人印象深刻的精神纪录。耶鲁 医学院以及其内科和免疫生物学部门将提供 资源，支持和基础设施，以协助Goldman-Israelow博士实现此处描述的目标 提案及其长期目标是发展为独立的身体科学家，研究规则 控制病毒感染和疫苗接种的抗体发展。