PanCorVac (Center for Pan-Coronavirus Vaccine Development)

PanCorVac（泛冠状病毒疫苗开发中心）

• 批准号: 10841731
• 负责人: YOSHIHIRO KAWAOKA
• 金额: $ 461.82万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10841731
• 关键词: 2019-nCoV; Affinity; Animal Model; Animals; Antibodies; Antibody Response; Antigens; B-Lymphocytes; Bacteriophages; CD8-Positive T-Lymphocytes; CD8B1 gene; COVID-19 pandemic; COVID-19 vaccine; Capsid Proteins; Cellular Immunity; Cohort Studies; Complement; Coronavirus; Data; Development; Epitopes; Evaluation; Face; Funding; Generations; Genes; Goals; Head; Human; Immune; Immune response; Immunization; Immunize; Immunodominant Epitopes; Immunoglobulins; Immunology; Individual; Infection; Influenza; Institution; Japanese; Knowledge; Longitudinal cohort study; Maintenance; Memory B-Lymphocyte; Mesocricetus auratus; Messenger RNA; Methods; Mission; Modification; Molecular Virology; Monoclonal Antibodies; Mus; Mutate; National Institute of Allergy and Infectious Disease; Persons; Phenotype; Plasma Cells; Population; Prevention; Preventive vaccine; Property; Proteins; Public Health; Reaction; Research; Research Personnel; Research Project Grants; SARS coronavirus; SARS-CoV-2 antigen; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Sampling; Sequence Homology; Serum; Specificity; Structure of germinal center of lymph node; T cell response; T-Lymphocyte; T-Lymphocyte Epitopes; Technology; Testing; Transgenic Mice; United States National Institutes of Health; Vaccinated; Vaccination; Vaccinee; Vaccines; Viral Proteins; Virus; Virus-like particle; candidate selection; combat; coronavirus receptor; coronavirus vaccine; cross reactivity; design; high throughput analysis; human coronavirus; immunogenic; immunogenicity; innovation; lipid nanoparticle; long term memory; nanobiotechnology; neutralizing antibody; novel; novel strategies; novel vaccines; pandemic coronavirus; pandemic disease; pandemic potential; post SARS-CoV-2 infection; protective efficacy; receptor; response; self assembly; single cell technology; stem; structural biology; universal coronavirus vaccine; vaccine candidate; vaccine development; vaccine platform; viral transmission; zoonotic coronavirus

SUMMARY Most of the vaccines currently approved or in development against the pandemic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus target immunodominant, strain-specific epitopes in the SARS-CoV-2 spike (S) protein and are therefore not expected to confer protection against other coronaviruses. Accordingly, the NIAID announced NOT-AI-21-002, which calls for the “development of prophylactic vaccines to provide broad and durable protection against coronaviruses, especially SARS-CoV-2 and others with pandemic potential”. In response to this call, we assembled the Pan-Coronavirus Vaccine (PanCoVac) consortium to develop and test novel pan-coronavirus vaccines. Research Project 1 (RP1; Design and evaluation of pan- CoV vaccines) uses two strategies to develop broadly protective coronavirus vaccines: (i) Focus immune responses away from the immunodominant epitopes in the head region of S and towards the more conserved, immune-subdominant epitopes in the stem region of S; and (ii) Refocus immune responses from the variable immunodominant epitopes towards more conserved epitopes in the head region of S. For each strategy, several innovative approaches will be used. Novel antigens will be presented by virus-like particles based on a self- assembling bacteriophage coat protein (a highly immunogenic platform). The candidate vaccines will be tested for their immunogenicity and protective efficacy against different coronaviruses in an animal model. Selected candidates will be tested in a second animal model, and with an mRNA lipid nanoparticle platform. Additional studies will test the durability of immune responses and the effect of vaccination on virus transmission. Samples from vaccinated animals will be provided to Research Project 2 (RP2; Immunological responses to pan-CoV vaccines) for a detailed assessment of B- and T-cell responses. First, RP2 will continue its ongoing efforts to generate and characterize panels of SARS-CoV S-specific mAbs, which will be used in RP1 to help characterize and prioritize vaccine candidates. Moreover, “Ig-omics”, which involves single-cell technologies allowing high- throughput analysis of B-cell responses, phenotypes, immunoglobulin (Ig) repertoires and mAbs that react to several coronaviruses (a technology developed by one of the RP2 investigators), will be used to characterize B cell-mediated immunity and mAb specificity induced by the candidate vaccines. RP2 will also test (and compare with data from a human cohort study) the ability of the candidate vaccines to elicit responses to cross-reactive CD4 and CD8 T cell epitopes. In particular, recently developed novel methods will be used to characterize and compare the T-cell repertoires upon infection and vaccination. An Administrative Core will oversee and manage all financial and administrative aspects of the consortium. Our proposed research draws strength from a multi- institutional team of experts in molecular virology, structural biology, nanobiotechnology, and B- and T-cell immunology.

概括 目前批准或开发出针对大流行SARS-COV-2的大多数疫苗（严重的急性 呼吸综合征冠状病毒2）病毒靶标免疫主导，菌株特异性表位SARS-COV-2 尖峰蛋白，因此预计不会赋予其他冠状病毒的保护。根据 NIAID宣布了不是-AI-21-002，它要求“开发预防性疫苗以提供 对冠状病毒，尤其是SARS-COV-2和其他大流行的广泛而持久的保护 潜在的”。为了回应这个电话，我们组装了泛氧化病毒疫苗（Pancovac）财团 开发和测试新型泛氧化病毒疫苗。研究项目1（RP1；泛图设计和评估 COV疫苗）使用两种策略来开发广泛保护的冠状病毒疫苗：（i）重点免疫 反应远离S头部区域的免疫主流表位，并降低了更保守的， S茎区域中的免疫表位； （ii）从变量中重新聚焦免疫反应 免疫主导的表位朝向S的头部区域中更保守的表位。对于每种策略，几个 将使用创新的方法。新型抗原将由病毒样颗粒基于自我 组装噬菌体外套蛋白（一种高度免疫原性平台）。候选疫苗将进行测试 因为它们的免疫原性和保护动物模型中不同冠状病毒的效率。选定 候选物将在第二个动物模型和mRNA脂质纳米颗粒平台中进行测试。额外的 研究将测试免疫调查的耐用性以及疫苗接种对病毒传播的影响。样品 从接种疫苗的动物将提供研究2（RP2；对Pan-COV的免疫反应 疫苗）用于对B和T细胞反应的详细评估。首先，RP2将继续其持续的努力 生成和表征SARS-COV S特异性mAb的面板，将在RP1中使用来帮助表征 并确定候选疫苗的优先级。此外，“ Ig-omics”涉及单细胞技术，允许高 B细胞反应，表型，免疫球蛋白（Ig）曲目和对反应的mAb的吞吐量分析 几种冠状病毒（一名RP2研究者开发的技术）将用于表征B 候选疫苗诱导的细胞介导的免疫和MAB特异性。 RP2也将测试（并比较 通过人类队列研究的数据）候选疫苗引起对交叉反应的反应的能力 CD4和CD8 T细胞表位。特别是，最近开发的新颖方法将用于表征和 比较感染和疫苗接种后的T细胞库。行政核心将监督和管理 财团的所有财务和行政方面。我们提出的研究从多数 分子病毒学，结构生物学，纳米生物技术以及B-和T细胞专家的机构团队 免疫学。

项目成果

Recombinant spike protein vaccines coupled with adjuvants that have different modes of action induce protective immunity against SARS-CoV-2.

• DOI: 10.1016/j.vaccine.2023.08.054
• 发表时间: 2023-08
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: S. Chiba;P. Halfmann;S. Iida;Yuichiro Hirata;Yuko Sato;M. Kuroda;T. Armbrust;Sam Spyra;Tadaki Suzuki;Y. Kawaoka

Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses.

• DOI: 10.1016/j.ebiom.2022.104341
• 发表时间: 2022-12
• 期刊: EBIOMEDICINE
• 影响因子: 11.1
• 作者: Halfmann, Peter J.;Frey, Steven J.;Loef, Kathryn;Kuroda, Makoto;Maemura, Tadashi;Armbrust, Tammy;Yang, Jie E.;Hou, Yixuan J.;Baric, Ralph;Wright, Elizabeth R.;Kawaoka, Yoshihiro;Kane, Ravi S.
• 通讯作者: Kane, Ravi S.