Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of TuberculosisReportar como inadecuado




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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.



Autor: Timothy Lahey , Dominick Laddy, Krystal Hill, Jacqueline Schaeffer, Alison Hogg, James Keeble, Belinda Dagg, Mei Mei Ho, Robert D

Fuente: http://plos.srce.hr/



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