Novel particulate vaccines utilizing polyester nanoparticles (bio-beads) for protection against Mycobacterium bovis...

Bovine tuberculosis (TB) continues to be a major health problem in cattle and development of a safe effective vaccine to control TB in cattle would be very useful. This paper reviews progress and provides new data in development of a TB bio-bead vaccine based on polyester nanoparticle inclusions which were produced by bioengineered bacteria. Polyhydroxybutyrate (PHB) biopolyester nanoparticles (bio-beads) have been produced which displayed mycobacterial antigens, Ag85A and ESAT-6, on the surface of the bio-beads for use as vaccines for the control of tuberculosis. Bio-beads were purified from the host production bacteria, Escherichia coli and the generally regarded as safe (GRAS) bacterium, Lactococcus lactis. Previous published studies showed that vaccination with Ag85A/ESAT-6 bio-beads induced antigen-specific IFN-γ, IL-17A, IL-6, TNF-α and IL-2 in splenocytes, but no significant increase in IL-4, IL-5 or IL-10. New results showed that antigen-specific IFN-γ release was induced by both CD4 and CD8 T cells in mice vaccinated with the Ag85A/ESAT-6 bio-beads. Mice vaccinated with Ag85A/ESAT-6 bio-beads alone or in combination with BCG had significantly lower bacterial counts from the lungs and spleen following aerosol challenge with Mycobacterium bovis compared to control groups. This unique approach to the design and production of bacterial-derived bio-beads displaying antigens enables a cost-effective way to express a diverse antigen repertoire for use as vaccines to combat TB or other diseases.