A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

Vaccines
Carolyn M ShoenD S Kernodle

Abstract

Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-v...Continue Reading

References

Jul 1, 1979·Journal of Biological Standardization·H FreudensteinH Schweinsberg
Aug 1, 1988·The American Review of Respiratory Disease·G W Comstock
Sep 26, 1966·Archives of Biochemistry and Biophysics·C A WoolfolkE R Stadtman
Jun 5, 1983·Journal of Molecular Biology·D Hanahan
Dec 1, 1995·Journal of Leukocyte Biology·J E Albina
Sep 20, 1997·Nature·M A Behr, P M Small
Jan 1, 1997·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·E R RhoadesI M Orme
Jan 16, 1999·Free Radical Biology & Medicine·K RutaultD R Katz
Feb 29, 2000·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·T OettingerP Andersen
Jun 30, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·G W Comstock
Dec 26, 2001·American Journal of Respiratory and Critical Care Medicine·K M EdwardsD S Kernodle
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Deepak KaushalWilliam R Bishai
Dec 12, 2002·Methods in Enzymology·Miriam BraunsteinWilliam R Jacobs
May 1, 1958·A.M.A. Archives of Internal Medicine·J D ARONSONH C TAYLOR
May 6, 2004·JAMA : the Journal of the American Medical Association·Naomi E AronsonLee H Harrison
Jun 10, 2004·Cellular Microbiology·Florian WinauUlrich E Schaible
Jul 22, 2004·Journal of Neuroimmunology·Roel C van der VeenFlorence M Hofman
Feb 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Glenn TullyMarkus J Maeurer
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Isabelle VergneVojo Deretic
Jul 14, 2005·Nature Reviews. Microbiology·Peter Andersen, T Mark Doherty
Oct 8, 2005·American Journal of Respiratory and Critical Care Medicine·Claudia CarranzaStephan K Schwander

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Citations

Nov 28, 2017·PLoS Pathogens·Stephen M CarpenterSamuel M Behar

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Methods Mentioned

BETA
genetic modifications
PCR
electrophoresis

Software Mentioned

Aeras
Adobe Photoshop
Adobe Illustrator
GraphPad
Prism

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