IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Skinner, M. A.
Right arrow Articles by Glyn Hewinson, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Skinner, M. A.
Right arrow Articles by Glyn Hewinson, R.

 Previous Article  |  Next Article 

Infection and Immunity, September 2003, p. 4901-4907, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4901-4907.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A DNA Prime-Mycobacterium bovis BCG Boost Vaccination Strategy for Cattle Induces Protection against Bovine Tuberculosis{dagger}

Margot A. Skinner,1* Bryce M. Buddle,1 D. Neil Wedlock,1 Denise Keen,1 Geoffrey W. de Lisle,1 Ricardo E. Tascon,2 Jose Candido Ferraz,2 Douglas B. Lowrie,2 Paul J. Cockle,3 H. Martin Vordermeier,3 and R. Glyn Hewinson3

AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand,1 The National Institute for Medical Research, Mill Hill, London,2 Veterinary Laboratory Agency, Weybridge, Surrey, United Kingdom3

Received 24 February 2003/ Returned for modification 26 March 2003/ Accepted 10 June 2003

The variable efficacy of bacillus Calmette-Guérin (Mycobacterium bovis BCG) in protecting humans and cattle against tuberculosis has prompted a search for a more effective vaccination regimen. A prime-boost strategy was investigated in cattle naturally sensitized to environmental mycobacteria by using a combination of three DNA vaccines coding for Hsp 65, Hsp 70, and Apa for priming, followed by a boost with BCG prior to experimental challenge with virulent M. bovis. Controls were vaccinated with DNA or BCG alone or were not vaccinated. The immune responses were monitored throughout the study, and protection was assessed based on reductions in the numbers of lesions and viable mycobacteria in lymph node samples. Vaccination with BCG alone or with a DNA prime-BCG boost regimen induced high levels of antigen-specific gamma interferon (IFN-{gamma}) in whole-blood cultures. In the prime-boost group there were fewer animals with severe lung lesions, fewer lymph nodes with lesions per animal, a smaller proportion of animals with lesions, lower mean lung and lymph node lesion scores, and less M. bovis isolated from retropharyngeal and thoracic lymph nodes compared to the results obtained for the nonvaccinated animals. The prime-boost regimen induced significant enhancement of protection in six parameters, compared with significant enhancement of protection in only two parameters for BCG alone. In addition, following challenge, in vitro IFN-{gamma} responses against ESAT-6 and CFP-10, as well as bovine tuberculin-induced skin test and in vitro IFN-{gamma} responses, were identified as immunological markers that predicted protection. The use of the prime-boost strategy suggested that a combination of vaccines may be better than a single vaccine for protection against tuberculosis.

* Corresponding author. Mailing address: AgResearch, Wallaceville Animal Research Centre, P.O. Box 40-063, Upper Hutt, New Zealand. Phone: 64 4 9221304. Fax: 64 4 922 1380. E-mail: margot.skinner{at}agresearch.co.nz.

{dagger} We dedicate this paper to Jo Colson (1948-2003), who encouraged and supported this work and made a significant contribution to tuberculosis research.

Editor: S. H. E. Kaufmann

Infection and Immunity, September 2003, p. 4901-4907, Vol. 71, No. 9
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.9.4901-4907.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2003 by the American Society for Microbiology. All rights reserved.