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VaxCelerate: the use of MTBhsp70-avidin as an adjuvant to rapidly generate self-assembling vaccines with biotinylated, antigen-specific peptides targeting emerging pathogens. (VAC6P.941)

Jordan Fishman, Leonard Moise, Pierre LeBlanc, Timothy Brauns, Eric Berg, Daniel Richer, Christine Boyle, Anne De Groot, Bill Martin, David Baker, Brandon Zeigler, Dale Mais, William Taylor, Russell Coleman, Warren Shaw, Jeffrey Gelfand and Mark Poznansky
J Immunol May 1, 2014, 192 (1 Supplement) 140.2;
Jordan Fishman
121st Century Biochemicals, Inc., Marlborough, MA
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Leonard Moise
2EpiVax, Providence, RI
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Pierre LeBlanc
3Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, MA
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Timothy Brauns
3Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, MA
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Eric Berg
121st Century Biochemicals, Inc., Marlborough, MA
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Daniel Richer
3Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, MA
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Christine Boyle
2EpiVax, Providence, RI
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Anne De Groot
2EpiVax, Providence, RI
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Bill Martin
2EpiVax, Providence, RI
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David Baker
5University of Washington, Seattle, WA
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Brandon Zeigler
6MPI Research, Mattawan, MI
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Dale Mais
6MPI Research, Mattawan, MI
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William Taylor
7Pfenex, San Diego, CA
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Russell Coleman
7Pfenex, San Diego, CA
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Warren Shaw
4Pediatric and Infectious Diseases, Massachusetts General Hospital, Boston, MA
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Jeffrey Gelfand
3Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, MA
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Mark Poznansky
3Vaccine and Immunotherapy Center, Massachusetts General Hospital, Charlestown, MA
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Abstract

Development of effective vaccines against emerging infectious diseases can take years 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. The VaxCelerate Project’s goal is to create a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 days. A self-assembling vaccine, consisting of a fusion protein M. tuberculosis MTBhsp70 and avidin (MAV), is at the core of the approach. Mixing the MAV with biotinylated pathogen specific immunogenic peptides yields a self-assembled vaccine (SAV). To minimize the time required, we used a distributed R&D model involving experts in protein engineering, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing. This approach was first tested using ovalbumin in C57Bl/6 mice, Flu (H1N1) specific peptides, and ultimately a Lassa fever virus (LFV) specific vaccine in transgenic HLA DR3 mice. Using a GLP validated assay we demonstrated that the MAV assembled LFV induced significantly increased class II peptide specific interferon-CD4+ T cell responses in transgenic mice compared to peptide or MAV alone controls. The use of an identical design for each vaccine may facilitate accelerated regulatory review and by developing safety assessment tools that are more relevant to human vaccine responses than current preclinical models.

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The Journal of Immunology
Vol. 192, Issue 1 Supplement
1 May 2014
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VaxCelerate: the use of MTBhsp70-avidin as an adjuvant to rapidly generate self-assembling vaccines with biotinylated, antigen-specific peptides targeting emerging pathogens. (VAC6P.941)
Jordan Fishman, Leonard Moise, Pierre LeBlanc, Timothy Brauns, Eric Berg, Daniel Richer, Christine Boyle, Anne De Groot, Bill Martin, David Baker, Brandon Zeigler, Dale Mais, William Taylor, Russell Coleman, Warren Shaw, Jeffrey Gelfand, Mark Poznansky
The Journal of Immunology May 1, 2014, 192 (1 Supplement) 140.2;

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VaxCelerate: the use of MTBhsp70-avidin as an adjuvant to rapidly generate self-assembling vaccines with biotinylated, antigen-specific peptides targeting emerging pathogens. (VAC6P.941)
Jordan Fishman, Leonard Moise, Pierre LeBlanc, Timothy Brauns, Eric Berg, Daniel Richer, Christine Boyle, Anne De Groot, Bill Martin, David Baker, Brandon Zeigler, Dale Mais, William Taylor, Russell Coleman, Warren Shaw, Jeffrey Gelfand, Mark Poznansky
The Journal of Immunology May 1, 2014, 192 (1 Supplement) 140.2;
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  • Novel small molecule nucleotide homologs (SMNH) activate human macrophages to kill intracellular Mycobacterium tuberculosis. (VAC6P.949)
  • Differential contribution of variable heavy and variable light chain domains in viral epitope recognition and neutralization function (VAC6P.950)
  • Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo (VAC6P.951)
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Print ISSN 0022-1767        Online ISSN 1550-6606