Vaccination of Cattle with a CpG Oligodeoxynucleotide-Formulated Mycobacterial Protein Vaccine and<i>Mycobacterium bovis</i>BCG Induces Levels of Protection against Bovine Tuberculosis Superior to Those Induced by Vaccination with BCG Alone

Wedlock, D. Neil; Michel, Denis; Skinner, Margot A.; Koach, Jessica; Lisle, Geoffrey W. de; Vordermeier, H. Martin; Hewinson, R. Glyn; Hurk, Sylvia van Drunen Littel‐van den; Babiuk, Lorne A.; Hecker, Rolf; Buddle, Bryce M.

doi:10.1128/iai.73.6.3540-3546.2005

Cited by 62 publications

(54 citation statements)

References 34 publications

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“…bovis bacillus Calmette-Guérin (BCG) is associated with variable efficacy both in humans and in cattle, and a major research effort has been directed at improving both the efficacy and reliability of BCG (10,15). Heterologous prime-boost strategies based on the combination of BCG with either DNA vaccines, proteins, or live attenuated viruses have been developed to improve the efficacy of BCG vaccination against TB (9,22,23,33,43). In particular, boosting with recombinant attenuated viruses such as modified vaccinia virus Ankara (MVA) expressing the mycobacterial protective antigen Ag85A (Rv3804c), designated MVA85A, in conjunction with BCG priming has shown promise in animal models (13,22,46,47).…”

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Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection against Bovine Tuberculosis

et al. 2009

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Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.More than 50 million cattle are infected with Mycobacterium bovis, resulting in economic losses of approximately $3 billion annually (34). Over the last two decades, in Great Britain, failure of the (tuberculin) test-and-slaughter strategy has resulted in a dramatic rise in the incidence of tuberculosis (TB) in cattle (19). The urgent need for new and improved cattle vaccines and diagnostic reagents has been acknowledged by the British government, and development of a cattle vaccine is a research priority. As cattle can be considered a large-animal model for human TB vaccination, experiments with cattle will

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Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection against Bovine Tuberculosis

et al. 2009

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“…None of these vaccines were significantly more potent than BCG and some were less potent, including a DNA 13 vaccine that was found to be equivalent to BCG in an inbred mouse model but clearly inferior to BCG in the more stringent guinea pig model [26,27]. The most impressive vaccine regimens reported have utilized a DNA prime or a prime comprising M. bovis culture filtrate in a CpG oligodeoxynucleotide-containing adjuvant and a BCG boost; these prime-boost vaccine regimens showed a trend toward improvement over BCG in several parameters studied in cattle [29,31].…”

Section: Rbcg30 and Rbcg30mb-immunized Animals Exhibit Greater Protecmentioning

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A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG

Horwitz

Harth

Dillon

et al. 2006

Vaccine

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Mycobacterium bovis infection of cattle and other domesticated animals exacts a significant economic toll in both economically developing and industrialized countries. Vaccination of herds and/or wild animals that share their grazing land and serve as reservoirs of infection has been proposed as a strategy to combat bovine tuberculosis. However, the only currently available vaccine, M. bovis BCG, is not highly efficacious. Here we show that a live recombinant vaccine, rBCG30, which expresses large amounts of the Mycobacterium tuberculosis 30 kDa major secretory protein, is more efficacious against bovine tuberculosis than BCG in the highly demanding guinea pig model of pulmonary tuberculosis.

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“…Thus, the British government has acknowledged the urgent need for an effective vaccine. Current promising vaccines are based on heterologous primeboost approaches that include the live attenuated M. bovis vaccine strain bacillus Calmette-Guérin (BCG) (14,(16)(17)(18)(19). However, BCG vaccination sensitizes the animal to bovine tuberculin and compromises the specificity of the tuberculin tests currently used for diagnosis of BTB.…”

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Improved Skin Test for Differential Diagnosis of Bovine Tuberculosis by the Addition of Rv3020c-Derived Peptides

Jones

Whelan

Clifford

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTA peptide cocktail derived from the mycobacterial antigens ESAT-6, CFP-10, and Rv3615c allowed differentiation betweenMycobacterium bovis-infected and M. bovis bacillus Calmette-Guérin (BCG)-vaccinated cattle when used as a skin test reagent for a “DIVA” test (i.e., a test capable ofdifferentiatinginfected and uninfectedvaccinatedanimals). Addition of the antigen Rv3020c improves the diagnostic sensitivity without compromising specificity in the face of BCG or Johne's disease vaccination.

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Vaccination of Cattle with a CpG Oligodeoxynucleotide-Formulated Mycobacterial Protein Vaccine andMycobacterium bovisBCG Induces Levels of Protection against Bovine Tuberculosis Superior to Those Induced by Vaccination with BCG Alone

Cited by 62 publications

References 34 publications

Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection against Bovine Tuberculosis

Viral Booster Vaccines Improve Mycobacterium bovis BCG-Induced Protection against Bovine Tuberculosis

A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG

Improved Skin Test for Differential Diagnosis of Bovine Tuberculosis by the Addition of Rv3020c-Derived Peptides

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