Naturally attenuated, orally administered Mycobacterium microti as a tuberculosis vaccine is better than subcutaneous Mycobacterium bovis BCG

Infect Immun. 2002 Mar;70(3):1566-70. doi: 10.1128/IAI.70.3.1566-1570.2002.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Arvicolinae
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / therapeutic use*
  • Drug Administration Routes
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mycobacterium / immunology*
  • Mycobacterium bovis / immunology*
  • Species Specificity
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccination*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / therapeutic use


  • BCG Vaccine
  • Vaccines, Attenuated