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Protective Efficacy of BCG Overexpressing an L,D-Transpeptidase against M. tuberculosis Infection
Authors
A Demissie
A Shafferman
+49Β more
A Wright
AH Ding
AM Cooper
AM Dannenberg
AS Pym
B Saviola
CK Stover
DF Hoft
DN Wedlock
DR Sherman
E Girardi
GB Marks
GF Black
GF Hatfull
Gyanu Lamichhane
H Kavanagh
HD Park
IM Orme
IM Orme
JB Amberson
JC Betts
JL Flynn
JL Flynn
JT van Dissel
K Bhatt
Katy C. Kao
L Brandt
L Grode
LF Barker
LG Wayne
M Lavollay
MA Fisher
MA Horwitz
MI Voskuil
PA Selwyn
PE Fine
R Gupta
R Sun
RJ Dubos
RM Jasmer
Scott T. Nolan
SL Davis
T Maniatis
TB Clarke
TD Schmittgen
VK Sambandamurthy
WHO
WW Stead
YQ Qie
Publication date
1 January 2010
Publisher
Public Library of Science
Doi
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on
PubMed
Abstract
Background: M. bovis Bacille Calmette-GuΓ©rin (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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Last time updated on 05/06/2019
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info:doi/10.1371%2Fjournal.pon...
Last time updated on 01/04/2019