TY - JOUR
T1 - Protective efficacy of BCG overexpressing an L,D-transpeptidase against M. tuberculosisinfection
AU - Nolan, Scott T.
AU - Lamichhane, Gyanu
PY - 2010
Y1 - 2010
N2 - Background: M. bovis Bacille Calmette-Guérin (BCG), currently the only available vaccine against tuberculosis (TB), fails to adequately protect individuals from active and latent TB infection. New vaccines are desperately needed to decrease the worldwide burden of TB. Methods and Findings: We created a recombinant strain of BCG that overproduces an L,D-transpeptidase in order to alter the bacterial peptidoglycan layer and consequently increase the ability of this immunogen to protect against virulent M. tuberculosis (Mtb). We demonstrate that this novel recombinant BCG protects mice against virulent Mtb at least as well as control BCG, as measured by its ability to reduce bacterial burden in lungs and spleen, reduce lung histopathology, and prolong survival. A nutrient starved recombinant BCG preparation, while offering comparable protection, elicited a response characterized by elevated levels of select Th1 cytokines. Conclusions: Recombinant BCG overexpressing a L,D-transpeptidase that is nutrient starved elicits a stronger Th1 type response and is at least as protective as parent BCG. Results from this study suggest that nutrient starvation treatment of live BCG vaccines should be further investigated as a way to increase host induction of Th-1 related cytokines in the development of experimental anti-TB vaccines.
AB - Background: M. bovis Bacille Calmette-Guérin (BCG), currently the only available vaccine against tuberculosis (TB), fails to adequately protect individuals from active and latent TB infection. New vaccines are desperately needed to decrease the worldwide burden of TB. Methods and Findings: We created a recombinant strain of BCG that overproduces an L,D-transpeptidase in order to alter the bacterial peptidoglycan layer and consequently increase the ability of this immunogen to protect against virulent M. tuberculosis (Mtb). We demonstrate that this novel recombinant BCG protects mice against virulent Mtb at least as well as control BCG, as measured by its ability to reduce bacterial burden in lungs and spleen, reduce lung histopathology, and prolong survival. A nutrient starved recombinant BCG preparation, while offering comparable protection, elicited a response characterized by elevated levels of select Th1 cytokines. Conclusions: Recombinant BCG overexpressing a L,D-transpeptidase that is nutrient starved elicits a stronger Th1 type response and is at least as protective as parent BCG. Results from this study suggest that nutrient starvation treatment of live BCG vaccines should be further investigated as a way to increase host induction of Th-1 related cytokines in the development of experimental anti-TB vaccines.
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U2 - 10.1371/journal.pone.0013773
DO - 10.1371/journal.pone.0013773
M3 - Article
C2 - 21048936
AN - SCOPUS:78149446042
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 10
M1 - e13773
ER -