Journal article
Developing an epitope-driven tuberculosis (TB) vaccine
Vaccine, v 23(17), pp 2121-2131
2005
PMID: 15755582
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Epitope-driven vaccines are created from selected sub-sequences of proteins, or epitopes, derived by scanning the protein sequences of pathogens for patterns of amino acids that permit binding to human MHC molecules. We developed a prototype tuberculosis (TB) vaccine that contains epitopes derived by (1) EpiMer mapping of previously published secreted proteins derived from
Mycobacterium tuberculosis (Mtb), and (2) EpiMatrix mapping of selected Mtb genome open reading frames (ORFs). Each of the epitopes contains at least three distinct class II MHC binding motif matches. These Mtb epitope selections were validated by measuring T cell responses from peripheral blood mononuclear cells (PBMC) obtained from healthy, asymptomatic tuberculin skin test-positive donors. Twenty-four validated Mtb epitopes were selected for inclusion in a DNA plasmid vector. We immunized HLA-DR B*0101 transgenic mice with this vaccine prototype augmented by co-administration of rIL-15. Following administration of three immunizations at 14-day intervals in conjunction with rIL-15, epitope-specific T cell responses were observed to eight of the 24 epitopes contained in the DNA construct, one week following the last injection. The systematic application of bioinformatics tools to whole genomes, in combination with in vitro methods for screening and confirming epitopes, may lead to the development of novel vaccines for infectious diseases like TB.
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Details
- Title
- Developing an epitope-driven tuberculosis (TB) vaccine
- Creators
- Anne S De Groot - EpiVax, Inc., Providence, RI 02903, USAJulie McMurry - EpiVax, Inc., Providence, RI 02903, USALuisa Marcon - University of Padua, ItalyJudith Franco - University of Padua, ItalyDaniel Rivera - EpiVax, Inc., Providence, RI 02903, USAMichele Kutzler - University of Pennsylvania, Philadelphia, PA, USADavid Weiner - University of Pennsylvania, Philadelphia, PA, USABill Martin - EpiVax, Inc., Providence, RI 02903, USA
- Publication Details
- Vaccine, v 23(17), pp 2121-2131
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000227898700020
- Scopus ID
- 2-s2.0-14844336287
- Other Identifier
- 991014877983904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental