Integrative Immunogen Design and Testing
综合免疫原设计和测试
基本信息
- 批准号:10328121
- 负责人:
- 金额:$ 262.89万
- 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-LymphocytesChiropteraCoronavirusCoronavirus InfectionsCoronavirus spike proteinDetectionDevelopmentDiagnosticDisease OutbreaksDissociationEngineeringEnsureEpitopesEvaluationGenerationsGenetic VariationGoalsHIV-2HamstersHandHealthHumanImmune TargetingImmune responseImmunityInfectionLiteratureMeasuresMediatingMiddle East Respiratory SyndromeMiddle East Respiratory Syndrome CoronavirusModelingMolecular ConformationMusMutationPathogenicityPatternPolysaccharidesPositioning AttributeProteinsResistanceSARS coronavirusSevere Acute Respiratory SyndromeStructureT-LymphocyteTestingVaccinatedVaccinesVariantVirionVirusZoonosescold temperaturecombatcoronavirus vaccinecross reactivitycross-species transmissiondesignefficacy evaluationglycosylationhuman coronavirusimmunogenicityimprovedinnovationneutralizing antibodynovelnovel coronavirusparticlepressureprogramsreceptor bindingresponsethermostabilitytooltransmission processvaccine 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
冠状病毒很可能仍然是对人类健康的持续威胁。然而,下一步是否意义重大
疾病暴发将由一种已知的冠状病毒、另一种新的冠状病毒或持续激增的
SARS-CoV-2的变种(S)未知。这个项目的目标是开发新的、改进的免疫原来
诱导更广泛的抗冠状病毒免疫,从结构上评估所产生的泛冠状病毒或广谱冠状病毒
抗体,并评估广泛的冠状病毒疫苗在动物模型中的效果。我们将从小说开始
与早期版本相比,第三代峰值更好地保留在融合前的四元组中
文献中所描述的钉状物。这些新的尖峰蛋白被称为VFLIP,保留了一个三聚体
即使在没有外源三聚基序的情况下,构象也抵抗热变性,
具有更好地反映正宗病毒粒子上的糖结构并提供受体结合结构域位置的特征糖结构
构象也更好地反映了天然病毒粒子上的构象。这些分子的“关闭”速度更慢。
广泛的抗冠状病毒抗体的比率。在这个项目中,我们将从
这些改进的尖峰单独存在,并作为创新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的B细胞和T细胞免疫反应的能力。到时候我们会的
评价最佳候选免疫原在小鼠和仓鼠感染模型中的疗效
相关冠状病毒。该项目代表了协作、迭代循环的开始和结束
免疫基因的设计和评估。深入评估和迭代的周期将引领疫苗努力
针对冠状病毒构成的日益增长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
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
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
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:
$ 262.89万 - 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:
$ 262.89万 - 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:
$ 262.89万 - 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:
$ 262.89万 - 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:
$ 262.89万 - 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:
$ 262.89万 - 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:
$ 262.89万 - 项目类别:
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