| Characterization of novel multi-antigenic vaccine candidates with pan-HLA coverage against M. tuberculosis. | |
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MedLine Citation:
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PMID: 23283639 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Low protection of Calmette-Guérin (BCG) vaccine and drug-resistant strains require better anti-Mycobacterium tuberculosis (MTb) vaccines with a broad, long lasting, antigen-specific response. Using bioinformatics tools, we identified five 19-40mer signal peptide (SP) domain vaccine candidates (VCs) derived from MTb antigens.All VCs were predicted to have promiscuous binding to major histocompatibility complex (MHC) class I and II alleles in large geographic territories worldwide. Peripheral mononuclear cells (PBMC) from healthy naïve donors and tuberculosis patients exhibited strong proliferation that correlated positively with Th1 cytokine secretion only in healthy naïve donors. Proliferation to SP VCs was superior to antigen-matched control peptides with similar length and various MHC class I and II binding properties. T-cell lines induced to SP VCs from healthy naïve donors had increased CD44(high)/CD62L+ activation/effector memory markers and IFN-gamma, but not IL-4 production in both CD4+ and CD8+ T-cell subpopulations. T-cell lines from healthy naïve donors and tuberculosis patients also manifested strong, dose-dependent, antigen-specific cytotoxicity against autologous VC-loaded or MTb-infected macrophages. Lysis of MTb-infected targets was accompanied by high IFN-gamma secretion. Various combinations of these five VCs manifested synergic proliferation of PBMC from selected healthy naïve donors. Immunogenicity of the best three combinations, termed Mix1, Mix2 and Mix3, consisting of 2-5 of the VCs was then evaluated in mice. Each mixture manifested strong cytotoxicity against MTb-infected macrophages, while Mix3 also manifested VC-specific humoral immune response. Based on these results, we plan to evaluate the protection properties of these combinations as an improved tuberculosis subunit vaccine. |
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Authors:
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Riva Kovjazin; David Shitrit; Rachel Preiss; Ilanit Haim; Lev Triezer; Leonardo Fuks; Abdel Rahman Nader; Meir Raz; Ritta Bardenstein; Galit Horn; Nechama I Smorodinsky; Lior Carmon |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-2 |
Journal Detail:
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Title: Clinical and vaccine immunology : CVI Volume: - ISSN: 1556-679X ISO Abbreviation: Clin. Vaccine Immunol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101252125 Medline TA: Clin Vaccine Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Vaxil BioTherapeutics Ltd., Bl. 13A, 13 Einstein Street, Weizmann Science Park, Nes Ziona, Israel 74036. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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