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.

总结

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.