Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis

• Published in: PloS one 2016-12, Vol.11 (12), p.e0168521-e0168521
• Main Authors: Lahey, Timothy, Laddy, Dominick, Hill, Krystal, Schaeffer, Jacqueline, Hogg, Alison, Keeble, James, Dagg, Belinda, Ho, Mei Mei, Arbeit, Robert D, von Reyn, C Fordham
• Format: Article
• Language: English
• Subjects: Adults; Aerosols; Animal models; Animals; Antigens; Antigens, Bacterial; Bacillus Calmette-Guerin vaccine; Bacteriology; BCG; BCG Vaccine - immunology; BCG Vaccine - pharmacology; Biology and Life Sciences; Cell culture; Disease Models, Animal; Drug dosages; Effectiveness; Enzyme-linked immunosorbent assay; Experiments; Female; Global health; HIV; Homology; Human immunodeficiency virus; Humans; Humoral immunity; Immune response; Immunity; Immunization; Immunization, Secondary; Immunogenicity; Immunogenicity, Vaccine; Immunology; Interferon; Laboratory animals; Lentivirus; Lungs; Medical research; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mycobacterium; Mycobacterium bovis; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Pain; Pathogens; Patient outcomes; Prevention; Public health; Research and Analysis Methods; Retroviridae; Spleen; Testing; Tuberculin; Tuberculosis; Tuberculosis - immunology; Tuberculosis - prevention & control; Vaccination; Vaccines; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168521

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. 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. 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). DAR-901 induces cellular and humoral immunity and boosts protection from M. tuberculosis compared to a homologous BCG boost.