Document Detail


Characterization of novel multiantigenic vaccine candidates with pan-HLA coverage against Mycobacterium tuberculosis.
MedLine Citation:
PMID:  23283639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis 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 that 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 gamma interferon (IFN-γ), but not interleukin-4 (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 M. tuberculosis-infected macrophages. Lysis of M. tuberculosis-infected targets was accompanied by high IFN-γ 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 and consisting of 2 to 5 of the VCs, was then evaluated in mice. Each mixture manifested strong cytotoxicity against M. tuberculosis-infected macrophages, while Mix3 also manifested a 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.
Authors:
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:
Type:  Journal Article     Date:  2013-01-02
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  20     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-08-19     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  328-40     Citation Subset:  IM    
Affiliation:
Vaxil BioTherapeutics Ltd., Nes Ziona, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Bacterial / immunology*
Cell Proliferation
Cytokines / secretion
Cytotoxicity, Immunologic
Female
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class II / immunology*
Humans
Leukocytes, Mononuclear / immunology
Male
Mice
Mice, Inbred BALB C
Mycobacterium tuberculosis / immunology*
T-Lymphocyte Subsets / immunology
Tuberculosis Vaccines / administration & dosage,  immunology*
Chemical
Reg. No./Substance:
0/Antigens, Bacterial; 0/Cytokines; 0/Histocompatibility Antigens Class I; 0/Histocompatibility Antigens Class II; 0/Tuberculosis Vaccines
Comments/Corrections

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