Epitopes described in "Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein."

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
Article Title:Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein.
Reference Detail
Reference ID:1004728
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.
Affiliations:Corixa Corp., Seattle, WA 98104, USA. yskriky@aeras.org
Reference Type:Literature
PubMed ID:15187142
Journal:J Immunol
Journal Volume:172
Article Pages:7618-28
Journal ISSN:0022-1767
Article Chemical List:Adjuvants, Immunologic;Bacterial Proteins;DNA, Bacterial;Polyproteins;Tuberculosis Vaccines;Vaccines, DNA;Vaccines, Synthetic
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
Curation Last Updated:2015-07-30 20:16:11