Oral Vaccination of Guinea Pigs with a<i>Mycobacterium bovis</i>Bacillus Calmette-Guérin Vaccine in a Lipid Matrix Protects against Aerosol Infection with Virulent<i>M. bovis</i>

Clark, Simon; Cross, Martin L.; Nadian, Allan K.; Vipond, Julia; Court, Pinar; Williams, Ann; Hewinson, R. Glyn; Aldwell, Frank E.; Chambers, Mark A.

doi:10.1128/iai.00052-08

Cited by 24 publications

(20 citation statements)

References 43 publications

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“…Previous studies in mice, guinea pigs and possums showed oral encapsulated BCG gave superior protection to unformulated oral BCG (Clark et al, 2008). We wanted to make this comparison in badgers.…”

Section: Introductionmentioning

confidence: 94%

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

Chambers

Aldwell

Williams

et al. 2017

Front. Cell. Infect. Microbiol.

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The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease.

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Section: Introductionmentioning

confidence: 94%

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

Chambers

Aldwell

Williams

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Despite the opportunities to study infection caused by Mycobacterium bovis in the natural hosts (e.g., cattle and deer), guinea pigs have proven useful as an experimental tool to develop diagnostic skin test reagents (van Pinxteren et al 2000), screen mutants (Collins 2001), or perform early-stage down-selection of vaccines intended for use in cattle or wildlife (De Lisle et al 1999;Chambers et al 2002;Clark et al 2008).…”

Section: Studies Of Mycobacterium Bovis Infectionmentioning

confidence: 99%

Animal Models of Tuberculosis: Guinea Pigs

Clark

Hall

Williams

2014

Cold Spring Harbor Perspectives in Medicine

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“…Studies in several animal models have shown that formulating the BCG vaccine in adjuvant enhances its capacity to induce antituberculosis protective immunity (6)(7)(8)(9)(10)(11). Although the biological reasons for the enhanced immunogenicity of lipid-encapsulated BCG have not been fully defined, recent reports have suggested possible mechanisms for the increased vaccine-induced immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, a potentially simpler and less expensive strategy involves formulating BCG in a liposome-forming adjuvant. Lipid encapsulation of BCG has been shown to improve the immunogenicity and protective efficacy of BCG immunization in mice, guinea pigs, badgers, and cattle (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice

Derrick

Yabe

Morris

et al. 2016

Clin Vaccine Immunol

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Despite the widespread use of Mycobacterium bovis BCG vaccine and the availability of effective chemotherapy, tuberculosis (TB) remains an immense global public health challenge, with approximately 9 million new cases and 1.4 million deaths per year. Overall, an estimated 2 billion people are infected with M. tuberculosis worldwide (1, 2). These alarming statistics have made it obvious that current interventions are not controlling the epidemic. The reasons for the current TB problem are multifaceted and include the lack of an efficacious vaccine and the emergence of multidrug-resistant and extremely drug-resistant M. tuberculosis strains (1, 3). Importantly, the convergence of the HIV and TB epidemics has, without question, intensified the TB problem. Since HIV-infected individuals are considerably more susceptible to pathogens due to their immunocompromised state, coinfected individuals are 30 times more likely to develop active TB than those infected with M. tuberculosis only. In fact, TB causes 25% of all HIV-related deaths worldwide (2).While BCG is one of the most widely used global vaccines, its impact on the current TB epidemic has clearly been inadequate. Randomized controlled clinical trials and retrospective case-control studies have shown that BCG immunization is effective in reducing cases of severe disseminated TB in children; however, the effectiveness of BCG in preventing pulmonary TB has been highly variable, ranging from 0% to 80% (4). Furthermore, protection is often not highly persistent, with substantial waning of BCG-induced protective responses generally seen during the first decade after immunization (5). Given the suboptimal efficacy in the context of the devastating TB epidemic, there is an urgent global health need to develop a new TB immunization strategy. Consequently, many TB researchers are developing strategies to amplify BCG-induced antituberculosis protective responses. A popular approach involves boosting with protein-or virus-vectored vaccines after a priming BCG immunization. Alternatively, a potentially simpler and less expensive strategy involves formulating BCG in a liposome-forming adjuvant. Lipid encapsulation of BCG has been shown to improve the immunogenicity and protective efficacy of BCG immunization in mice, guinea pigs, badgers, and cattle (6-10).Our group recently demonstrated that formulation of a BCG⌬mmaA4 (BCG-A4) mutant in DDA/TDB adjuvant (A4/ Adj) increased the level and persistence of BCG-induced immune responses relative to those produced by conventional BCG and

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Oral Vaccination of Guinea Pigs with aMycobacterium bovisBacillus Calmette-Guérin Vaccine in a Lipid Matrix Protects against Aerosol Infection with VirulentM. bovis

Abstract: Increased incidence of bovine tuberculosis (TB) in the United Kingdom caused by infection with

Cited by 24 publications

References 43 publications

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

Animal Models of Tuberculosis: Guinea Pigs

Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice

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