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Infection and Immunity, November 2003, p. 6411-6419, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6411-6419.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Revaccination of Neonatal Calves with Mycobacterium bovis BCG Reduces the Level of Protection against Bovine Tuberculosis Induced by a Single Vaccination

B. M. Buddle,* D. N. Wedlock, N. A. Parlane, L. A. L. Corner,{dagger} G. W. de Lisle, and M. A. Skinner

AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand

Received 24 March 2003/ Returned for modification 15 May 2003/ Accepted 5 August 2003

Cattle may provide a suitable model for testing ways of improving tuberculosis vaccine efficacy in human infants. A vaccination and challenge study was undertaken in calves to determine the optimal time to vaccinate neonatal animals with Mycobacterium bovis bacillus Calmette-Guérin (BCG) for protection against tuberculosis and to determine whether revaccination with BCG was beneficial. Calves (10 per group) were vaccinated with BCG within 8 h of birth or at 6 weeks of age, when immune responses to antigens of environmental mycobacteria were detectable, or vaccinated at birth and revaccinated at 6 weeks. A control group was not vaccinated. BCG vaccination at birth induced strong antigen-specific gamma interferon (IFN-{gamma}) and interleukin-2 (IL-2) responses and antigen-specific activation in CD4+, CD8+, and WC1+ {gamma}{delta} T-cell subsets from blood. The proportions of animals per group with macroscopic tuberculous lesions after challenge were 0/10 for BCG at birth, 1/9 for BCG at 6 weeks, 4/10 for the revaccinated group, and 10/10 for the nonvaccinated group. There was no significant difference in the levels of protection between groups vaccinated at birth or at 6 weeks, while animals vaccinated both at birth and at 6 weeks had significantly less protection than those vaccinated only at birth. The revaccinated calves that subsequently developed tuberculous lesions had significantly stronger IFN-{gamma} and IL-2 responses to bovine purified protein derivative after the BCG booster than those in the same group that did not develop lesions. The results indicated that BCG vaccination at birth induced a high level of immunity and that the sensitization of very young animals to antigens of environmental mycobacteria by 6 weeks of age did not affect the effectiveness of BCG. However, BCG revaccination of these young animals was contraindicated.

* Corresponding author. Mailing address: AgResearch, Wallaceville Animal Research Centre, P.O. Box 40063, Upper Hutt, New Zealand. Phone: 64 4 9221418. Fax: 64 4 9221380. E-mail: bryce.buddle{at}agresearch.co.nz.

Editor: S. H. E. Kaufmann

{dagger} Present address: Department of Large Animal Clinical Sciences, Faculty of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland.

Infection and Immunity, November 2003, p. 6411-6419, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6411-6419.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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