Development of effective
vaccines against
emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready
vaccines before the EID has spread extensively. Lassa is a prototypical
emerging infectious disease endemic to West Africa for which no successful
vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid
vaccine development by creating a platform capable of generating and pre-clinically testing a new
vaccine against specific pathogen targets in less than 120 d A self-assembling
vaccine is at the core of the approach. It consists of a fusion
protein composed of the immunostimulatory Mycobacterium tuberculosis
heat shock protein 70 (MtbHSP70) and the
biotin binding protein,
avidin. Mixing the resulting
protein (MAV) with biotinylated pathogen-specific immunogenic
peptides yields a self-assembled
vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of
protein engineering and production, bioinformatics,
peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1
influenza specific
peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting
Lassa fever virus. We demonstrated that the
Lassa fever vaccine induced significantly increased class II
peptide specific
interferon-γ CD4(+) T cell responses in
HLA-DR3 transgenic mice compared to
peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each
vaccine and by applying safety and efficacy assessment tools that are more relevant to human
vaccine responses than current animal models.