Rationally Designed Pan-Ebolavirus Vaccine

Information

  • Research Project
  • 9697762
  • ApplicationId
    9697762
  • Core Project Number
    R01AI132204
  • Full Project Number
    5R01AI132204-03
  • Serial Number
    132204
  • FOA Number
    RFA-AI-16-047
  • Sub Project Id
  • Project Start Date
    6/20/2017 - 7 years ago
  • Project End Date
    5/31/2022 - 2 years ago
  • Program Officer Name
    REPIK, PATRICIA M
  • Budget Start Date
    6/1/2019 - 5 years ago
  • Budget End Date
    5/31/2020 - 4 years ago
  • Fiscal Year
    2019
  • Support Year
    03
  • Suffix
  • Award Notice Date
    5/13/2019 - 5 years ago

Rationally Designed Pan-Ebolavirus Vaccine

The Filoviridae family contains multiple highly pathogenic viruses that cause hemorrhagic fever in humans. Outbreaks of Ebola, Sudan, Bundibugyo, and Marburg viruses are unpredictable, can spread rapidly, and occur with 40-90% human lethality. Vaccination efforts for the Zaire ebolavirus (EBOV) show tremendous promise. The candidate vaccines, however, provides no protection against the other filoviruses with equivalent outbreak potential. We and others have recently identified two epitopes on Ebola virus glycoprotein (GP) that elicit antibodies that cross- react with, neutralize, and protect against other all ebolaviruses in animal models. These epitopes are not shared with the much more abundant, secreted soluble GP (sGP), which may serve as an antibody decoy during infection. Here, we propose to use structure-guided design to engineer immunogens that preferentially display these unique GP-specific (i.e. non-sGP), critical, and highly conserved structures and elicit high levels of such broadly-neutralizing and broadly protective antibodies against these epitopes. This three-PI program combines the expertise of (1) a pioneer in the field of structure-based and epitope-focused vaccine design, (2) the structural biologist who has determined most filovirus GP-antibody structures and handles the majority of the world?s filovirus antibodies, and (3) a leading expert in filovirus vaccines and immunology. In this highly collaborative program, iterative stages of innovative design and functional evaluation will lead to novel immunogens that could be used alone or in a prime-boost regimen with single-virus vaccines currently in clinical trials. Milestones along the way demonstrate progress in provision of novel structures, design of stable and immunogenic features, and elicitation of broadly-reactive and broadly- protective immune responses against the array of filovirus threats. The proposed program is designed to deliver a vaccine with demonstrated efficacy against Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus infections in guinea pig and ferret models as well as efficacy in NHP models of Sudan and Ebola virus infections.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R01
  • Administering IC
    AI
  • Application Type
    5
  • Direct Cost Amount
    1112448
  • Indirect Cost Amount
    134133
  • Total Cost
    1246581
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:1246581\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZAI1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    INTEGRATED BIOTHERAPEUTICS, INC.
  • Organization Department
  • Organization DUNS
    601000750
  • Organization City
    ROCKVILLE
  • Organization State
    MD
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    208503855
  • Organization District
    UNITED STATES