Previous Article | Next Article 
Infection and Immunity, February 2009, p. 622-631, Vol. 77, No. 2
0019-9567/09/$08.00+0 doi:10.1128/IAI.00685-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant 
ureC hly+ Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis
Elma Z. Tchilian,1,
*
Christiane Desel,2,
Emily K. Forbes,1
Silke Bandermann,2
Clare R. Sander,1
Adrian V. S. Hill,1
Helen McShane,1,
and
Stefan H. E. Kaufmann2,*
The Jenner Institute, Oxford University, ORCRB, Roosevelt Drive, Headington, Oxford OX3 7DQ, United Kingdom,1 Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany2
Received 31 May 2008/ Returned for modification 15 September 2008/ Accepted 26 November 2008
In the light of the recent emergence of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, the epidemic of tuberculosis (TB) in populations coinfected with human immunodeficiency virus, and the failure of Mycobacterium bovis bacillus Calmette-Guerin (BCG) to protect against disease, new vaccines against TB are urgently needed. Two promising new vaccine candidates are the recombinant 
ureC hly+ BCG (recBCG), which has been developed to replace the current BCG vaccine strain, and modified vaccinia virus Ankara (MVA) expressing M. tuberculosis antigen 85A (MVA85A), which is a leading candidate vaccine designed to boost the protective efficacy of BCG. In the present study, we examined the effect of MVA85A boosting on the protection afforded at 12 weeks postchallenge by BCG and recBCG by using bacterial CFU as an efficacy readout. recBCG-immunized mice were significantly better protected against aerosol challenge with M. tuberculosis than mice immunized with the parental strain of BCG. Intradermal boosting with MVA85A did not reduce the bacterial burden any further. In order to identify a marker for the development of a protective immune response against M. tuberculosis challenge, we analyzed splenocytes after priming or prime-boosting by using intracytoplasmic cytokine staining and assays for cytokine secretion. Boosting with MVA85A, but not priming with BCG or recBCG, greatly increased the antigen 85A-specific T-cell response, suggesting that the mechanism of protection may differ from that against BCG or recBCG. We show that the numbers of systemic multifunctional cytokine-producing cells did not correlate with protection against aerosol challenge in BALB/c mice. This emphasizes the need for new biomarkers for the evaluation of TB vaccine efficacy.
* Corresponding author. Mailing address for Elma Z. Tchilian (for experiments performed in Oxford): The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, United Kingdom. Phone: 44-1865-271247. Fax: 44-1865-281531. E-mail: elma.tchilian{at}ndm.ox.ac.uk. Mailing address for Stefan H. E. Kaufmann (for experiments performed in Berlin): Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany. Phone: 49/30-28460-500. Fax: 49/30-28460-501. E-mail: kaufmann{at}mpiib-berlin.mpg.de
Published ahead of print on 8 December 2008.
E. Z. Tchilian and C. Desel are joint first authors.
H. McShane and S. H. E. Kaufmann are joint senior authors.
Infection and Immunity, February 2009, p. 622-631, Vol. 77, No. 2
0019-9567/09/$08.00+0 doi:10.1128/IAI.00685-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»