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

基本信息

项目摘要

Project 2: SUMMARY The filoviruses, including multiple ebolaviruses and two marburgviruses, have emerged over 30 times to cause outbreaks of severe disease with high mortality. The epidemic potential of these viruses is demonstrated by the 2013-2016 outbreak, which spread from a single infected toddler to 28,000 cases across multiple nations. No therapeutic interventions are yet approved for filovirus infections, and there remains an urgent need for efficacious treatments. In this academic and industry collaboration, we will advance both specific- and broadly reactive monoclonal antibody (mAb) treatments that we have already shown to provide complete protection in non-human primates. Importantly, this study builds upon results of a global collaboration, the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC), that yielded the most comprehensive dataset for anti-Ebola virus mAbs yet assembled. From that comprehensive study, we learned additional correlates of mAb-mediated protection and built improved, multivariate computational models, which predict treatment combinations that maximize antibody features that most strongly predict in vivo protection (including Fc-mediated effector functions, Fc glycoforms, and neutralization). Additional treatment combinations, one Ebola virus-specific and one broadly cross-reactive, predicted by that detailed study may offer even greater efficacy than the two already in hand. Using our therapeutic candidates and additional well-characterized VIC mAbs as controls, we will evaluate thresholds of protection and correlates of protection across standard and innovative animal models. On a broader level, this study will illuminate how faithfully particular mAb features (e.g., Fab-driven neutralization, species- specific Fc-driven protection) translate across animal models used to satisfy the FDA “two-animal rule” for therapeutic approval. We will further use innovative high-throughput technologies, standard cell-based assays, targeted glycoforms and a library of well-characterized Fc substitutions to optimize both Fv and Fc to enhance protective activity. For this project, we have engaged a multidisciplinary team of experts in structural biology, virology, immunology, in vivo evaluation in animal models, computer modeling and statistical analysis, and industrial mAb production and development. Our translational research program is informed by data that are more comprehensive than any previously available, will forward optimized therapeutic candidates against multiple viruses with epidemic potential, and will help establish a broadly applicable platform to treat filoviruses and other infectious diseases.
项目2:概要 丝状病毒,包括多种埃博拉病毒和两种马尔堡病毒,已经出现了30多次, 严重疾病的爆发和高死亡率。这些病毒的流行潜力是由 2013年至2016年爆发,从一名受感染的幼儿蔓延到多个国家的28,000例病例。没有 治疗性干预措施尚未被批准用于丝状病毒感染,并且仍然迫切需要 有效的治疗。在这次学术和行业合作中,我们将在具体和广泛的领域推进 反应性单克隆抗体(mAb)治疗,我们已经证明,提供完全的保护, 非人类灵长类动物重要的是,这项研究建立在全球合作的结果,病毒性出血 发热免疫联盟(维克),产生了最全面的抗埃博拉病毒数据集 mAb尚未组装。从这项全面的研究中,我们了解到单克隆抗体介导的 保护和建立改进的,多变量计算模型,预测治疗组合, 最大化最强预测体内保护的抗体特征(包括Fc介导的效应子功能, Fc糖型和中和)。其他治疗组合,一种是埃博拉病毒特异性的,一种是广泛的 交叉反应,预测详细的研究可能会提供更大的疗效比两个已经在手。 使用我们的治疗候选物和另外的充分表征的维克单克隆抗体作为对照,我们将评估 保护阈值和标准和创新动物模型之间的保护相关性。在更广泛的 水平,这项研究将阐明如何忠实特定的mAb功能(例如,Fab驱动的中和,物种- 特异性Fc驱动的保护)在用于满足FDA“双动物规则”的动物模型中翻译, 治疗批准。我们将进一步使用创新的高通量技术,标准的基于细胞的测定, 靶向糖型和充分表征的Fc置换文库,以优化Fv和Fc两者,从而增强 保护活动。对于这个项目,我们聘请了一个多学科的结构生物学专家团队, 病毒学、免疫学、动物模型体内评价、计算机建模和统计分析,以及 工业mAb生产和开发。我们的转化研究计划是由数据, 比以前任何可用的更全面,将提出优化的治疗候选人, 具有流行潜力的多种病毒,并将有助于建立一个广泛适用的平台来治疗丝状病毒 和其他传染病。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

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

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:
    $ 220.97万
  • 项目类别:
Integrative Immunogen Design and Testing
综合免疫原设计和测试
  • 批准号:
    10842890
  • 财政年份:
    2021
  • 资助金额:
    $ 220.97万
  • 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:
    $ 220.97万
  • 项目类别:
Integrative Immunogen Design and Testing
综合免疫原设计和测试
  • 批准号:
    10328121
  • 财政年份:
    2021
  • 资助金额:
    $ 220.97万
  • 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:
    $ 220.97万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10158452
  • 财政年份:
    2019
  • 资助金额:
    $ 220.97万
  • 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:
    $ 220.97万
  • 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:
    $ 220.97万
  • 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:
    $ 220.97万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10617743
  • 财政年份:
    2019
  • 资助金额:
    $ 220.97万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 220.97万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了