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Infection and Immunity, August 2009, p. 3364-3373, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00287-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

H. Martin Vordermeier,1* Bernardo Villarreal-Ramos,1,3 Paul J. Cockle,1 Martin McAulay,3 Shelley G. Rhodes,1 Tyler Thacker,5 Sarah C. Gilbert,2 Helen McShane,2 Adrian V. S. Hill,2 Zhou Xing,4 and R. Glyn Hewinson1

TB Research Group, Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom,1 The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom,2 Institute for Animal Health, Compton, Berkshire, United Kingdom,3 Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada,4 National Animal Disease Center, United States Department of Agriculture, Ames, Iowa5

Received 12 March 2009/ Returned for modification 6 May 2009/ Accepted 21 May 2009

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.

* Corresponding author. Mailing address: TB Research Group, VLA-Weybridge, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. Phone: 44 1932 357 884. Fax: 44 1932 357 260. E-mail: m.vordermeier{at}vla.defra.gsi.gov.uk

{triangledown} Published ahead of print on 1 June 2009.

Editor: R. P. Morrison

Infection and Immunity, August 2009, p. 3364-3373, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00287-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vordermeier, H. M., Dean, G. S., Rosenkrands, I., Agger, E. M., Andersen, P., Kaveh, D. A., Hewinson, R. G., Hogarth, P. J. (2009). Adjuvants Induce Distinct Immunological Phenotypes in a Bovine Tuberculosis Vaccine Model. CVI 16: 1443-1448 [Abstract] [Full Text]  


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