Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model
Ma. Horwitz et al., Recombinant bacillus Calmette-Guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model, P NAS US, 97(25), 2000, pp. 13853-13858
Citations number
37
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Tuberculosis (TB) continues to ravage humanity, causing 2 million deaths pe
r year. A vaccine against Tn more potent than the current live vaccine, bac
illus Calmette-Guerin (BCG). is desperately needed. Using two commercially
available strains of BCC as host strains, BCC Connaught and Tice, we have c
onstructed two recombinant BCC vaccines stably expressing and secreting the
30-kDa major secretory protein of Mycobacterium tuberculosis (M. tb.), the
primary causative agent of Tn. We have tested the efficacy of the two stra
ins in the highly susceptible guinea pig model of pulmonary TB, a model not
eworthy for its close resemblance to human TB. Animals immunized with the r
ecombinant BCG vaccines and challenged by aerosol with a highly Virulent st
rain of M. tb. had 0.5 logs fewer M. tb. bacilli in their lungs and 1 log f
ewer bacilli in their spleens on average than animals immunized with their
parental conventional BCG Vaccine counterparts. Statistically, these differ
ences were highly significant. Paralleling these results, at necropsy, anim
als immunized with the recombinant BCG vaccines had fewer and smaller lesio
ns in the lung, spleen, and liver and significantly less lung pathology tha
n animals immunized with the parental BCC vaccines. The recombinant Vaccine
s are the first Vaccines against TB more potent than the current commercial
ly available BCC vaccines, which were developed nearly a century ago.