title: Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein.
abstract: A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 T(H)1 response with high antibody titres with a IgG2a-bias and significant IFN-gamma production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-gamma responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. l.hall@ucc.ie
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Hall
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.forename: Simon O
authors.initials: SO
authors.lastname: Clark
authors.forename: Dominic L F
authors.initials: DL
authors.lastname: Kelly
authors.forename: Moataz Abd
authors.initials: MA
authors.lastname: El Ghany
authors.forename: Christine
authors.initials: C
authors.lastname: Hale
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marsh
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; C027538:heat-labile enterotoxin, E coli; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis