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

Simon Clark, Martin L. Cross, Alan Smith, Pinar Court, Julia Vipond, Allan Nadian, R. Glyn Hewinson, Hannah K. Batchelor, Yvonne Perrie, Ann Williams, Frank E. Aldwell, Mark A. Chambers

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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-γ) 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 106-107 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 107 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.

Original languageEnglish
Pages (from-to)5791-5797
Number of pages7
JournalVaccine
Volume26
Issue number46
Early online date26 Sep 2008
DOIs
Publication statusPublished - 29 Oct 2008
Externally publishedYes

Fingerprint

BCG Vaccine
Mycobacterium bovis
aerosols
Aerosols
Mustelidae
alginates
Rodentia
mouth
rodents
immune response
vaccines
badgers
Lipids
lipids
guinea pigs
Bovine Tuberculosis
Meles meles
Guinea Pigs
Vaccines
bovine tuberculosis

Cite this

Clark, Simon ; Cross, Martin L. ; Smith, Alan ; Court, Pinar ; Vipond, Julia ; Nadian, Allan ; Hewinson, R. Glyn ; Batchelor, Hannah K. ; Perrie, Yvonne ; Williams, Ann ; Aldwell, Frank E. ; Chambers, Mark A. / 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. In: Vaccine. 2008 ; Vol. 26, No. 46. pp. 5791-5797.
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abstract = "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-Gu{\'e}rin (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-γ) 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 106-107 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 107 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.",
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Clark, S, Cross, ML, Smith, A, Court, P, Vipond, J, Nadian, A, Hewinson, RG, Batchelor, HK, Perrie, Y, Williams, A, Aldwell, FE & Chambers, MA 2008, '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', Vaccine, vol. 26, no. 46, pp. 5791-5797. https://doi.org/10.1016/j.vaccine.2008.08.028

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. / Clark, Simon; Cross, Martin L.; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R. Glyn; Batchelor, Hannah K.; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E.; Chambers, Mark A.

In: Vaccine, Vol. 26, No. 46, 29.10.2008, p. 5791-5797.

Research output: Contribution to journalArticle

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AU - Clark, Simon

AU - Cross, Martin L.

AU - Smith, Alan

AU - Court, Pinar

AU - Vipond, Julia

AU - Nadian, Allan

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AU - Batchelor, Hannah K.

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AU - Williams, Ann

AU - Aldwell, Frank E.

AU - Chambers, Mark A.

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