title: Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis.
abstract: BACKGROUND
  The development of a novel tuberculosis vaccine is a leading global health priority. SRL172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase III trial in HIV-infected and BCG immunized adults in Tanzania. Here we describe the immunogenicity and protective efficacy of DAR-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.
  
  
  METHODS
  We evaluated IFN-γ responses by ELISpot and antibody responses by enzyme linked immunosorbent assay in C57BL/6 and BALB/c mice after three doses of DAR-901. In an aerosol challenge model, we evaluated the protective efficacy of the DAR-901 booster in C57BL/6 mice primed with BCG and boosted with two doses of DAR-901 at 4 dosage levels in comparison with homologous BCG boost.
  
  
  RESULTS
  DAR-901 vaccination elicited IFN-γ responses to mycobacterial antigen preparations derived from both DAR-901 and Mycobacterium tuberculosis. DAR-901 immunization enhanced antibody responses to DAR-901 but not Mycobacterium tuberculosis lysate or purified protein derivative. Among animals primed with BCG, boosting with DAR-901 at 1 mg provided greater protection against aerosol challenge than a homologous BCG boost (lungs P = 0.036, spleen P = 0.028).
  
  
  CONCLUSIONS
  DAR-901 induces cellular and humoral immunity and boosts protection from M. tuberculosis compared to a homologous BCG boost.
authors.affiliation: Dartmouth's Geisel School of Medicine, 1 Medical Center Drive, Lebanon, NH, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lahey
authors.affiliation: Aeras, 1405 Research Blvd. Rockville, MD United States of America.
authors.forename: Dominick
authors.initials: D
authors.lastname: Laddy
authors.affiliation: Aeras, 1405 Research Blvd. Rockville, MD United States of America.
authors.forename: Krystal
authors.initials: K
authors.lastname: Hill
authors.affiliation: Aeras, 1405 Research Blvd. Rockville, MD United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schaeffer
authors.affiliation: Aeras, 1405 Research Blvd. Rockville, MD United States of America.
authors.forename: Alison
authors.initials: A
authors.lastname: Hogg
authors.affiliation: Bacteriology Division, MHRA-NIBSC, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Keeble
authors.affiliation: Bacteriology Division, MHRA-NIBSC, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: Belinda
authors.initials: B
authors.lastname: Dagg
authors.affiliation: Bacteriology Division, MHRA-NIBSC, South Mimms, Potters Bar, Hertfordshire, United Kingdom.
authors.forename: Mei Mei
authors.initials: MM
authors.lastname: Ho
authors.affiliation: Tufts University School of Medicine, Boston, MA United States of America.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Arbeit
authors.affiliation: Dartmouth's Geisel School of Medicine, 1 Medical Center Drive, Lebanon, NH, United States of America.
authors.forename: C Fordham
authors.initials: CF
authors.lastname: von Reyn
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001500:BCG Vaccine / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine