Bioengineered bacterial
polyester inclusions have the potential to be used as a
vaccine delivery system. The biopolyester beads were engineered to display a fusion
protein of the
polyester synthase PhaC and the two key
antigens involved in immune response to the infectious agent that causes
tuberculosis, Mycobacterium tuberculosis, notably
antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis.
Polyester beads displaying the respective fusion
protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed
antigens was investigated. The beads were not toxic to the animals, as determined by
weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water
emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion
protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the
cytokine gamma interferon (Th1 immune response) and increased levels of
immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign
antigens represent a new class of versatile, safe, and biocompatible
vaccines.