Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.
Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.
Clark
Simon
S
Health Protection Agency, Porton Down, Salisbury SP4 0JG, United Kingdom.
Cross
Martin L
ML
Smith
Alan
A
Court
Pinar
P
Vipond
Julia
J
Nadian
Allan
A
Hewinson
R Glyn
RG
Batchelor
Hannah K
HK
Perrie
Yvonne
Y
Williams
Ann
A
Aldwell
Frank E
FE
Chambers
Mark A
MA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000284:Administration, Oral; D000336:Aerosols; D000464:Alginates; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D001835:Body Weight / Q000502:physiology; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D015169:Colony Count, Microbial; D004337:Drug Carriers; D005260:Female; D006168:Guinea Pigs; D008081:Liposomes; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016955:Moraxella bovis; D045828:Moraxellaceae Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D009929:Organ Size; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000336:Aerosols; D000464:Alginates; D001500:BCG Vaccine; D002214:Capsules; D004337:Drug Carriers; D008081:Liposomes