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:概述

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:
    $ 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:

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