| Title | Bacterial polyester inclusions engineered to display vaccine candidate antigens for use as a novel class of safe and efficient vaccine delivery agents. | | Author(s) | Parlane NA, Wedlock DN, Buddle BM, Rehm BH | | Institution | AgResearch, Hopkirk Research Institute, Palmerston North, New Zealand; Institute of Molecular Biosciences, Massey University, Palmerston North, New Zealand. | | Source | Appl Environ Microbiol 2009 Oct 16. | | Abstract | 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 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 immunity in mice to the displayed antigens was investigated. The beads were not toxic for the animals, as determined by weight gain and absence of lesions at the inoculation site in immunised 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 interferon-gamma (Th1 immune response) and increased levels of IgG1 (Th2 immune response). Hence engineered biopolyester beads displaying foreign antigens represent a new class of versatile safe and biocompatible vaccines. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19837843 |
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