Construction and efficacy testing of novel recombinant vaccine designs for eliciting both broadly neutralizing antibodies and T cells against Lassa virus

Information

  • Research Project
  • 9558223
  • ApplicationId
    9558223
  • Core Project Number
    R44AI138745
  • Full Project Number
    1R44AI138745-01
  • Serial Number
    138745
  • FOA Number
    PA-17-302
  • Sub Project Id
  • Project Start Date
    4/9/2018 - 6 years ago
  • Project End Date
    3/31/2019 - 5 years ago
  • Program Officer Name
    REPIK, PATRICIA M
  • Budget Start Date
    4/9/2018 - 6 years ago
  • Budget End Date
    3/31/2019 - 5 years ago
  • Fiscal Year
    2018
  • Support Year
    01
  • Suffix
  • Award Notice Date
    4/9/2018 - 6 years ago
Organizations

Construction and efficacy testing of novel recombinant vaccine designs for eliciting both broadly neutralizing antibodies and T cells against Lassa virus

PROJECT SUMMARY GeoVax, a clinical-stage biotechnology company focusing on vaccine development against infectious diseases and cancer, seeks to build on its successful vaccine candidate against Lassa virus (LASV) to implement a novel immunogen design for eliciting broadly cross-reactive neutralizing antibodies. LASV is a member of the Arenaviridae family and is endemic in West Africa where it infects 100,000-300,000 persons each year, with approximately 5,000 deaths. No vaccine is currently under clinical development for the prevention of LASV infection. GeoVax created a vaccine against LASV (GEO-LM01) using its proven Modified Vaccinia Ankara (MVA) Virus-Like Particle (VLP) platform. GEO-LM01 incorporates into the MVA genome LASV sequences encoding both a glycoprotein (GPC) and a matrix protein (Z). Upon infection of human cells, the MVA-driven expression of these proteins results in the budding from the surface of the infected cells of VLPs that bear natively-folded GPC on their surface. Pre-clinical testing of GEO-LM01 in a lethal mouse model demonstrated 100% protection after a single dose with strong T cell responses yet meagre antibody responses, in line with other vaccine candidates tested in animals. Capitalizing on recent breakthroughs in the structural characterization of LASV GPC, we propose in this Fast-Track Phase I/II application to develop and test novel GPC immunogen designs in the context of the MVA-VLP system. Phase I will consist of sequence design, MVA-VLP construction, in vitro testing, and efficacy and immunogenicity studies in an established lethal mouse model. In Phase II, GEO-LM01 and the selected new vaccine candidate will be produced at high titers and tested against all four major lineages of LASV in the established Hartley guinea pig challenge model. Both vaccines will then be tested for efficacy in non-human primates and will be concomitantly evaluated extensively for the magnitude and characteristics of the cellular and humoral immune responses. The final down-selected vaccine candidate will be tested for genetic stability and sterility in preparation for cGMP manufacturing and a Phase 1 clinical study.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R44
  • Administering IC
    AI
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    299820
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:299820\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    GEOVAX, INC.
  • Organization Department
  • Organization DUNS
    148374205
  • Organization City
    SMYRNA
  • Organization State
    GA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    300807648
  • Organization District
    UNITED STATES