title: Oral delivery of lipid-encapsulated Mycobacterium bovis BCG extends survival of the bacillus in vivo and induces a long-term protective immune response against tuberculosis.
abstract: The success of oral-route vaccination using Mycobacterium bovis bacille Calmette-Guérin (BCG) relies on delivery of live, actively metabolising bacilli to confer protection. Here, we describe that lipid-microencapsulation can extend the in vivo survival of bacilli when fed to mice, and can induce a long-lasting protective immune response. Feeding mice with lipid-encapsulated BCG (L-BCG) resulted in greater recovery of viable BCG bacilli from the mesenteric lymph nodes (MLN) compared to mice fed non-encapsulated BCG. A time-course study indicated persistence of viable BCG bacilli in MLN up to 30 weeks post-vaccination, similar to the duration of viable BCG recovery from the spleen following subcutaneous vaccination. The persistence of viable bacilli in the MLN of L-BCG mice invoked long-lasting systemic cell-mediated immune reactivity, with responses similar to those observed in subcutaneously-vaccinated mice. Further, L-BCG-vaccinated mice showed a high degree of protection against aerogenic challenge with virulent M. bovis at 30 weeks post-vaccination, with significant reductions in lung and spleen pathogen burdens. This study identifies that lipid-encapsulation of live BCG bacilli can facilitate increased in vivo survival and immunogenicity of the vaccine in orally-vaccinated mice, and highlights protection via this route for up to 7 months post-immunisation.
authors.affiliation: Department of Microbiology & Immunology, University of Otago, P.O. Box 56, Dunedin, New Zealand. frank.aldwell@stonebow.otago.ac.nz
authors.forename: F E
authors.initials: FE
authors.lastname: Aldwell
authors.forename: M L
authors.initials: ML
authors.lastname: Cross
authors.forename: C E
authors.initials: CE
authors.lastname: Fitzpatrick
authors.forename: M R
authors.initials: MR
authors.lastname: Lambeth
authors.forename: G W
authors.initials: GW
authors.lastname: de Lisle
authors.forename: B M
authors.initials: BM
authors.lastname: Buddle
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000284:Administration, Oral; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control* / Q000662:veterinary*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D008055:Lipids