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Infection and Immunity, March 2002, p. 1566-1570, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1566-1570.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Naturally Attenuated, Orally Administered Mycobacterium microti as a Tuberculosis Vaccine Is Better than Subcutaneous Mycobacterium bovis BCG

Yukari C. Manabe,1,,2* Cherise P. Scott,2 and William R. Bishai1,2

Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine,1 Department of International Health, Johns Hopkins University Bloombers School of Public Health, Baltimore, Maryland 212052

Received 5 September 2001/ Returned for modification 1 November 2001/ Accepted 3 December 2001

Mycobacterium microti is phylogenetically closely related to Mycobacterium tuberculosis and is a member of that complex of organisms. It is a curved, acid-fast bacillus that is naturally attenuated with a narrow host range for Microtus species only. In this study, we confirm the unique susceptibility of voles to infection with M. microti and the relative resistance of mice with a significantly lower organism burden after 8 weeks of infection. In addition, histopathologic examination of lungs reveals a lack of cellular, granulomatous aggregates characteristically seen in murine M. tuberculosis infection. In the past, M. microti has been used successfully in humans as a vaccine against tuberculosis but was associated with cutaneous reactions. In an attempt to circumvent this adverse effect, we report the efficacy of aerosol and oral vaccination with M. microti. High-dose orogastric vaccination with M. microti resulted in a statistically significant improvement in protection against aerosol challenge with virulent M. tuberculosis in the murine model compared with subcutaneous M. bovis BCG Pasteur vaccination.

* Corresponding author. Mailing address: Johns Hopkins University School of Medicine, 424 North Bond St., Rm. 108, Baltimore, MD 21205. Phone: (410) 614-6600. Fax: (410) 614-8173. E-mail: ymanabe{at}jhmi.edu.

Infection and Immunity, March 2002, p. 1566-1570, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1566-1570.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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  • Aldwell, F. E., Brandt, L., Fitzpatrick, C., Orme, I. M. (2005). Mice Fed Lipid-Encapsulated Mycobacterium bovis BCG Are Protected against Aerosol Challenge with Mycobacterium tuberculosis. Infect. Immun. 73: 1903-1905 [Abstract] [Full Text]  
  • Frota, C. C., Hunt, D. M., Buxton, R. S., Rickman, L., Hinds, J., Kremer, K., van Soolingen, D., Colston, M. J. (2004). Genome structure in the vole bacillus, Mycobacterium microti, a member of the Mycobacterium tuberculosis complex with a low virulence for humans. Microbiology 150: 1519-1527 [Abstract] [Full Text]  
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