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: Timothy Lahey, Dominick Laddy, Krystal Hill, Jacqueline Schaeffer, Alison Hogg, James Keeble, Belinda Dagg, Mei Mei Ho, Robert D Arbeit, C Fordham von Reyn
• Journal: PloS one (PLoS One) Vol. 11 Issue 12 Pg. e0168521 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27997597 (Publication Type: Journal Article)

Chemical References

• Antigens, Bacterial
• BCG Vaccine

Topics

• Animals
• Antigens, Bacterial
• BCG Vaccine (immunology, pharmacology)
• Disease Models, Animal
• Female
• Humans
• Immunization, Secondary
• Immunogenicity, Vaccine
• Mice
• Mice, Inbred BALB C
• Mycobacterium tuberculosis (immunology)
• Tuberculosis (immunology, prevention & control)