Immunization with hybrid recombinant Mycobacterium tuberculosis H37Rv proteins increases the TH1 cytokine response in mice following a pulmonary instillation of irradiated mycobacteria
Autor: | Heinz Gert de Couet, James T. Douglas, Osler A. Andres, Paul Q. Patek, Sandro Jube, Chad B. Walton, Dulal Borthakur, Ana Blossom H. Inos |
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Rok vydání: | 2008 |
Předmět: |
Immunogen
Recombinant Fusion Proteins Epitopes T-Lymphocyte CD8-Positive T-Lymphocytes Epitope Mycobacterium tuberculosis Mice Bacterial Proteins MHC class I Animals Tuberculosis Vaccines Lung Mice Inbred BALB C Mycobacterium bovis General Veterinary General Immunology and Microbiology biology Antigen processing Public Health Environmental and Occupational Health Cross-presentation Th1 Cells biology.organism_classification Molecular biology Mice Inbred C57BL Infectious Diseases biology.protein Cytokines Molecular Medicine Tuberculosis vaccines |
Zdroj: | Vaccine. 26:4396-4402 |
ISSN: | 0264-410X |
Popis: | The aim of this research was to identify subunit immunogens that can generate enhanced CD8 T cell and TH1 responses against Mycobacterium tuberculosis. A genomic comparison of the M. tuberculosis H(37)R(V) and M. bovis BCG identified 61 proteins that are unique to H(37)R(V). Further screening of these 61 proteins using in silico analyses mimicking proteasomal digestion, transporter-associated antigen processing and H-2 antigen presentation identified 13 proteins with high densities of predicted MHC class I epitopes. Two native proteins, Rv1986c and Rv3875, were selected on the basis of their secreted or transmembrane characteristics and relatively lower frequencies of predicted MHC class II epitopes. To further enhance the CD8 T cell and TH1 responses, a hybrid protein, H32, was constructed by combining the nucleotide sequences encoding the MHC class I antigen-rich segment of Rv1986c and the entire Rv3875 sequence. The two native proteins and the hybrid were used to immunize C57BL/6 and Balb/c mice, which was followed by pulmonary instillation with irradiated M. tuberculosis H(37)R(V). All three proteins elicited elevated IFN-gamma responses, with the hybrid showing significant increases over the native proteins in both mice. This strategy of immunogen selection might be used to improve the current subunit vaccines against M. tuberculosis as well as other intra-cellular pathogens. |
Databáze: | OpenAIRE |
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