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| Article Authors: | Yasir A W Skeiky; Mark R Alderson; Pamela J Ovendale; Jeffrey A Guderian; Lise Brandt; Davin C Dillon; Antonio Campos-Neto; Yves Lobet; Wilfried Dalemans; Ian M Orme; Steven G Reed |
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| Article Title: | Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. |
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| Reference ID: | 1004728 |
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| Abstract: | Key Ags of Mycobacterium tuberculosis initially identified in the context of host responses in healthy purified protein derivative-positive donors and infected C57BL/6 mice were prioritized for the development of a subunit vaccine against tuberculosis. Our lead construct, Mtb72F, codes for a 72-kDa polyprotein genetically linked in tandem in the linear order Mtb32(C)-Mtb39-Mtb32(N). Immunization of C57BL/6 mice with Mtb72F DNA resulted in the generation of IFN-gamma responses directed against the first two components of the polyprotein and a strong CD8(+) T cell response directed exclusively against Mtb32(C). In contrast, immunization of mice with Mtb72F protein formulated in the adjuvant AS02A resulted in the elicitation of a moderate IFN-gamma response and a weak CD8(+) T cell response to Mtb32c. However, immunization with a formulation of Mtb72F protein in AS01B adjuvant generated a comprehensive and robust immune response, resulting in the elicitation of strong IFN-gamma and Ab responses encompassing all three components of the polyprotein vaccine and a strong CD8(+) response directed against the same Mtb32(C) epitope identified by DNA immunization. All three forms of Mtb72F immunization resulted in the protection of C57BL/6 mice against aerosol challenge with a virulent strain of M. tuberculosis. Most importantly, immunization of guinea pigs with Mtb72F, delivered either as DNA or as a rAg-based vaccine, resulted in prolonged survival (>1 year) after aerosol challenge with virulent M. tuberculosis comparable to bacillus Calmette-Guérin immunization. Mtb72F in AS02A formulation is currently in phase I clinical trial, making it the first recombinant tuberculosis vaccine to be tested in humans. |
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| Affiliations: | Corixa Corp., Seattle, WA 98104, USA. yskriky@aeras.org |
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| Date: | 2004 |
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| Reference Type: | Literature |
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| PubMed ID: | 15187142 |
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| Journal: | J Immunol |
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| Journal Volume: | 172 |
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| Article Pages: | 7618-28 |
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| Journal ISSN: | 0022-1767 |
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| Article Chemical List: | Adjuvants, Immunologic;Bacterial Proteins;DNA, Bacterial;Polyproteins;Tuberculosis Vaccines;Vaccines, DNA;Vaccines, Synthetic |
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| Article MeSH List: | Adjuvants, Immunologic(therapeutic use ); Animals; Bacterial Proteins(administration & dosage; chemical synthesis ); Base Sequence; DNA, Bacterial(administration & dosage ); Female; Guinea Pigs; Immunity; Immunization(methods ); Mice; Mice, Inbred C57BL; Molecular Sequence Data; Mycobacterium tuberculosis(chemistry; genetics ); Polyproteins(chemical synthesis; immunology; therapeutic use ); Survival Rate; Tuberculosis Vaccines(administration & dosage; chemistry ); Tuberculosis, Pulmonary(prevention & control; therapy ); Vaccines, DNA; Vaccines, Synthetic |
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| Curation Last Updated: | 2009-11-09 19:30:51 |
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