Integrative Immunogen Design and Testing
综合免疫原设计和测试
基本信息
- 批准号:10842890
- 负责人:
- 金额:$ 206.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:2019-nCoVAnimal Disease ModelsAnimal ModelAnimalsAntibodiesAntibody ResponseAntigensB-LymphocytesChiropteraCollaborationsCoronavirusCoronavirus InfectionsCoronavirus spike proteinDetectionDevelopmentDisease OutbreaksDissociationEbolaEngineeringEnsureEpitopesEvaluationGenerationsGenetic VariationGoalsHIV-2HamstersHandHealthHumanImmune TargetingImmune responseImmunityInfectionLiteratureMeasuresMediatingMiddle East Respiratory SyndromeMiddle East Respiratory Syndrome CoronavirusModelingMolecular ConformationMusMutationPathogenicityPatternPolysaccharidesPositioning AttributeProteinsResistanceSARS coronavirusSARS-CoV-2 transmissionSARS-CoV-2 variantStructureT-LymphocyteTestingVaccinatedVaccinesVariantVirionVirusZoonosescold temperaturecombatcoronavirus vaccinecross immunitycross reactivitycross-species transmissiondesigndiagnostic toolefficacy evaluationglycosylationhuman coronavirusimmunogenicityimprovedinnovationneutralizing antibodynovelnovel coronavirusparticlepressureprogramsreceptor bindingresponsethermostabilityvaccine candidateviral fitness
项目摘要
Project 3 Summary
Coronaviruses will likely remain a persistent threat to human health. However, whether the next significant
disease outbreak will be caused by a known coronavirus, another novel coronavirus, or continued surges from
variant(s) of SARS-CoV-2 is unknown. The goal of this project is to develop novel, improved immunogens to
elicit broader anti-coronavirus immunity, to structurally evaluate resulting pan-coronavirus or broad-coronavirus
antibodies, and to evaluate efficacy of broad coronavirus vaccines in animal models. We will begin with novel
third-generation spikes that better remain in a pre-fusion quaternary assemblies relative to earlier versions of
spike that have been described in the literature. These novel spike proteins, termed “VFLIP”, retain a trimeric
conformation even in the absence of exogenous trimerization motifs, are resistant to thermal denaturation,
feature glycan structures that better reflect those on authentic virions and offer receptor-binding domain positions
and conformation that also better reflect those on native virions. These molecules further feature slower “off”
rates for a wide panel of anti-coronavirus antibodies. In this program, we will develop novel immunogens from
these improved spikes alone and as part of innovative multimeric vaccine particles. Our collaborating projects
will evaluate these immunogens for their ability to elicit broad B- and T-cell immune responses. We will then
evaluate the efficacy of the best candidate immunogens in mouse and hamster models of infection using multiple
relevant coronaviruses. This project represents the beginning and end of the collaborative, iterative circle of
immunogen design and evaluation. Cycles of in-depth evaluation and iteration will shepherd vaccine efforts for
broad protection against the growing threat posed by coronaviruses.
项目3摘要
冠状病毒可能仍然是对人类健康的持续威胁。然而,下一个重要的
疾病爆发将由一种已知的冠状病毒、另一种新型冠状病毒或
SARS-CoV-2的变种尚不清楚。该项目的目标是开发新的,改进的免疫原,
引发更广泛的抗冠状病毒免疫,以在结构上评估产生的泛冠状病毒或宽冠状病毒
抗体,并评估广泛的冠状病毒疫苗在动物模型中的效力。我们将开始与小说
第三代钉,相对于早期版本,
在文献中已经描述过的尖峰。这些新的刺突蛋白,被称为“VFLIP”,保留了三聚体结构。
即使在不存在外源三聚基序的情况下,构象也对热变性具有抗性,
特征聚糖结构,更好地反映了真实病毒体上的聚糖结构,并提供受体结合域位置
和构象也更好地反映了天然病毒体上的那些。这些分子的进一步特点是“关闭”较慢
广泛的抗冠状病毒抗体的比率。在这个项目中,我们将开发新的免疫原,
这些改进的刺突单独和作为创新的多聚体疫苗颗粒的一部分。我们的合作项目
将评估这些免疫原引发广泛B和T细胞免疫应答的能力。然后我们将
使用多重免疫学方法评价最佳候选免疫原在小鼠和仓鼠感染模型中的功效
相关的冠状病毒。这个项目代表了协作、迭代循环的开始和结束,
免疫原设计和评价。深入评价和反复的周期将指导疫苗工作,
针对冠状病毒带来的日益严重的威胁提供广泛的保护。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Erica Ollmann Saphire其他文献
Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae
- DOI:
10.1007/s00705-012-1454-0 - 发表时间:
2012-09-23 - 期刊:
- 影响因子:2.500
- 作者:
Jens H. Kuhn;Yiming Bao;Sina Bavari;Stephan Becker;Steven Bradfute;J. Rodney Brister;Alexander A. Bukreyev;Kartik Chandran;Robert A. Davey;Olga Dolnik;John M. Dye;Sven Enterlein;Lisa E. Hensley;Anna N. Honko;Peter B. Jahrling;Karl M. Johnson;Gary Kobinger;Eric M. Leroy;Mark S. Lever;Elke Mühlberger;Sergey V. Netesov;Gene G. Olinger;Gustavo Palacios;Jean L. Patterson;Janusz T. Paweska;Louise Pitt;Sheli R. Radoshitzky;Erica Ollmann Saphire;Sophie J. Smither;Robert Swanepoel;Jonathan S. Towner;Guido van der Groen;Viktor E. Volchkov;Victoria Wahl-Jensen;Travis K. Warren;Manfred Weidmann;Stuart T. Nichol - 通讯作者:
Stuart T. Nichol
A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein
针对 SARS-CoV-2 刺突蛋白的广泛抗体的系统分析的全球合作
- DOI:
10.1016/j.celrep.2025.115499 - 发表时间:
2025-04-22 - 期刊:
- 影响因子:6.900
- 作者:
Sharon L. Schendel;Xiaoying Yu;Peter J. Halfmann;Jarjapu Mahita;Brendan Ha;Kathryn M. Hastie;Haoyang Li;Daniel Bedinger;Camille Troup;Kan Li;Natalia Kuzmina;Jordi B. Torrelles;Jennifer E. Munt;Melissa Mattocks;Mary Osei-Twum;Heather M. Callaway;The CoVIC-DB Team;Stephen Reece;Anne Palser;Paul Kellam;S. Moses Dennison;Erica Ollmann Saphire - 通讯作者:
Erica Ollmann Saphire
The C-terminus of Sudan ebolavirus VP40 contains a functionally important CXsubn/subC motif, a target for redox modifications
苏丹埃博拉病毒 VP40 的 C 末端包含一个功能重要的 CXC 基序,这是氧化还原修饰的一个靶点。
- DOI:
10.1016/j.str.2023.06.004 - 发表时间:
2023-09-07 - 期刊:
- 影响因子:4.300
- 作者:
Anke-Dorothee Werner;Martin Schauflinger;Michael J. Norris;Michael Klüver;Anna Trodler;Astrid Herwig;Christina Brandstädter;Melissa Dillenberger;Gerhard Klebe;Andreas Heine;Erica Ollmann Saphire;Katja Becker;Stephan Becker - 通讯作者:
Stephan Becker
Infusion of neutralization into Lassa vaccine design
将中和作用注入拉沙疫苗设计中
- DOI:
10.1016/j.it.2025.05.006 - 发表时间:
2025-07-01 - 期刊:
- 影响因子:13.900
- 作者:
Haoyang Li;Kathryn M. Hastie;Erica Ollmann Saphire - 通讯作者:
Erica Ollmann Saphire
Recurring conformation of the human immunodeficiency virus type 1 gp120 V3 loop.
人类免疫缺陷病毒 1 型 gp120 V3 环的重复构象。
- DOI:
10.1016/s0042-6822(03)00525-7 - 发表时间:
2003 - 期刊:
- 影响因子:3.7
- 作者:
R. Stanfield;J. Ghiara;Erica Ollmann Saphire;A. Profy;I. Wilson - 通讯作者:
I. Wilson
Erica Ollmann Saphire的其他文献
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{{ truncateString('Erica Ollmann Saphire', 18)}}的其他基金
Structure of the SARS-CoV-2 Nucleocapsid: building block to viral capsid
SARS-CoV-2 核衣壳的结构:病毒衣壳的构建模块
- 批准号:
10728253 - 财政年份:2023
- 资助金额:
$ 206.09万 - 项目类别:
Consortium for Immunotherapeutics against Emerging Viral Threats
针对新兴病毒威胁的免疫治疗联盟
- 批准号:
10447562 - 财政年份:2021
- 资助金额:
$ 206.09万 - 项目类别:
Consortium for Immunotherapeutics against Emerging Viral Threats
针对新兴病毒威胁的免疫治疗联盟
- 批准号:
10199909 - 财政年份:2020
- 资助金额:
$ 206.09万 - 项目类别:
Specific and Broadly Active Monoclonal Antibody Therapeutics Against The Filoviruses
针对丝状病毒的特异性且广泛活性的单克隆抗体疗法
- 批准号:
10402338 - 财政年份:2019
- 资助金额:
$ 206.09万 - 项目类别:
Consortium for Immunotherapeutics against Emerging Viral Threats
针对新兴病毒威胁的免疫治疗联盟
- 批准号:
9924443 - 财政年份:2019
- 资助金额:
$ 206.09万 - 项目类别:
Specific and Broadly Active Monoclonal Antibody Therapeutics Against The Filoviruses
针对丝状病毒的特异性且广泛活性的单克隆抗体疗法
- 批准号:
10158448 - 财政年份:2019
- 资助金额:
$ 206.09万 - 项目类别:
Specific and Broadly Active Monoclonal Antibody Therapeutics Against The Filoviruses
针对丝状病毒的特异性且广泛活性的单克隆抗体疗法
- 批准号:
10617736 - 财政年份:2019
- 资助金额:
$ 206.09万 - 项目类别:
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