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The Protective Effect of the Mycobacterium bovis BCG Vaccine Is Increased by Coadministration with the Mycobacterium tuberculosis 72-Kilodalton Fusion Polyprotein Mtb72F in M. tuberculosis -Infected Guinea Pigs
Open accessAbstract
A tuberculosis vaccine candidate consisting of a 72-kDa polyprotein or fusion protein based upon the Mtb32 and Mtb39 antigens of Mycobacterium tuberculosis and designated Mtb72F was tested for its protective capacity as a potential adjunct to the Mycobacterium bovis BCG vaccine in the mouse and guinea pig models of this disease. Formulation of recombinant Mtb72F (rMtb72F) in an AS02A adjuvant enhanced the Th1 response to BCG in mice but did not further reduce the bacterial load in the lungs after aerosol challenge infection. In the more stringent guinea pig disease model, rMtb72F delivered by coadministration with BCG vaccination significantly improved the survival of these animals compared to BCG alone, with some animals still alive and healthy in their appearance at >100 weeks post-aerosol challenge. A similar trend was observed with guinea pigs in which BCG vaccination was boosted by DNA vaccination, although this increase was not statistically significant due to excellent protection conferred by BCG alone. Histological examination of the lungs of test animals indicated that while BCG controls eventually died from overwhelming lung consolidation, the majority of guinea pigs receiving BCG mixed with rMtb72F or boosted twice with Mtb72F DNA had mostly clear lungs with minimal granulomatous lesions. Lesions were still prominent in guinea pigs receiving BCG and the Mtb72F DNA boost, but there was considerable evidence of lesion healing and airway remodeling and reestablishment. These data support the hypothesis that the coadministration or boosting of BCG vaccination with Mtb72F may limit the lung consolidation seen with BCG alone and may promote lesion resolution and healing. Collectively, these data suggest that enhancing BCG is a valid vaccination strategy for tuberculosis that is worthy of clinical evaluation.
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Stoute, J. A., Slaoui, M., Heppner, D. G., Momin, P., Kester, K. E., Desmons, P., Wellde, B. T., Garçon, N., Krzych, U., Marchand, M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199701093360202 · Cited by 870
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The success and failure of BCG — implications for a novel tuberculosis vaccine
Andersen, P., & Doherty, T. M. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1211 · Cited by 788
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Duthie, M. S., Windish, H. P., Fox, C. B., & Reed, S. G. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00978.x · Cited by 437
Self-citationAnnulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis
Kaufmann, S. H. E., & McMichael, A. J. (2005) · Nature Medicine · doi:10.1038/nm1221 · Cited by 273
Location of Persisting Mycobacteria in a Guinea Pig Model of Tuberculosis Revealed by R207910
Lenaerts, A. J., Hoff, D., Aly, S., Ehlers, S., Andries, K., Cantarero, L., Orme, I. M., & Basaraba, R. J. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00276-07 · Cited by 257
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Metadata
- Authors
- Brandt, L., Skeiky, Y. A. W., Alderson, M. R., Lobet, Y., Dalemans, W., Turner, O. C., Basaraba, R. J., Izzo, A. A., Lasco, T. M., Chapman, P. L., Reed, S. G., & Orme, I. M.
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2004-11
- Volume
- 72
- Issue
- 11
- Pages
- 6622-6632
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- OpenAlex
- W2112772985
- Cited by
- 174
- References
- 1
- FWCI
- 10.17
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The Protective Effect of the Mycobacterium bovis BCG Vaccine Is Increased by Coadministration with the Mycobacterium tuberculosis 72-Kilodalton Fusion Polyprotein Mtb72F in M. tuberculosis -Infected Guinea Pigs. https://app.cochat.ai/papers/10.1128/iai.72.11.6622-6632.2004
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- Brandt, L., Skeiky, Y. A. W., Alderson, M. R., Lobet, Y., Dalemans, W., Turner, O. C., Basaraba, R. J., Izzo, A. A., Lasco, T. M., Chapman, P. L., Reed, S. G., & Orme, I. M. (2004). The Protective Effect of the Mycobacterium bovis BCG Vaccine Is Increased by Coadministration with the Mycobacterium tuberculosis 72-Kilodalton Fusion Polyprotein Mtb72F in M. tuberculosis -Infected Guinea Pigs. Infection and Immunity. https://doi.org/10.1128/iai.72.11.6622-6632.2004
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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