Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis

Scientific Reports
Ivan P NascimentoLuciana C C Leite

Abstract

In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0-3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently ...Continue Reading

References

Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·J HessS H Kaufmann
Jul 27, 1999·Nature·D B LowrieC L Silva
Apr 15, 2003·Nature Medicine·Alexander S PymStewart T Cole
May 17, 2005·Vaccine·Arun T KamathUNKNOWN World Health Organization
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jes DietrichPeter Andersen
Feb 27, 2007·Vaccine·Umesh Datta GuptaDavid N McMurray
Dec 2, 2008·Journal of Experimental & Clinical Cancer Research : CR·Daher C ChadePriscila M Andrade
Feb 10, 2009·The Journal of Infectious Diseases·Graham A W RookAlimuddin Zumla
Apr 8, 2009·Immunology and Cell Biology·Claus AagaardPeter Andersen
Jul 17, 2009·Clinical and Experimental Immunology·F Abebe, G Bjune
Oct 7, 2009·American Journal of Respiratory Cell and Molecular Biology·Ana P ChristMomtchilo Russo
Mar 2, 2010·Tuberculosis·Denise Morais FonsecaVânia Luiza Deperon Bonato
May 4, 2010·Journal of Internal Medicine·S H E Kaufmann
Jan 18, 2013·Human Vaccines & Immunotherapeutics·Carlos R Zárate-BladésCelio L Silva
Jan 22, 2013·Respirology : Official Journal of the Asian Pacific Society of Respirology·Charles C WangYing Zhang
Feb 22, 2013·The New England Journal of Medicine·Alimuddin ZumlaC Fordham von Reyn
Mar 23, 2013·Annual Review of Immunology·Anne O'GarraMatthew P R Berry
Jun 26, 2013·Human Vaccines & Immunotherapeutics·David A Hokey, Ann Ginsberg
Sep 12, 2013·Current Opinion in Immunology·Matthew Paul Reddoch BerryAnne O'Garra
Feb 26, 2014·BMC Infectious Diseases·Carlotta MontagnaniMaurizio de Martino
Mar 15, 2014·Current Opinion in Pulmonary Medicine·Stefan H E Kaufmann
Mar 19, 2014·Journal of Internal Medicine·J Weiner, S H E Kaufmann
Oct 24, 2015·Developmental and Comparative Immunology·Aiti VizziniMatteo Cammarata
Dec 16, 2016·Clinical and Vaccine Immunology : CVI·André G LoxtonUNKNOWN VPM Study Group

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Citations

Nov 2, 2019·Human Vaccines & Immunotherapeutics·Carina Carvalho Dos SantosIvan Pereira Nascimento
May 20, 2020·Memórias do Instituto Oswaldo Cruz·Larissa V NascimentoIvan P Nascimento
Feb 21, 2018·Frontiers in Immunology·Natalie E Nieuwenhuizen, Stefan H E Kaufmann
Aug 30, 2020·Disease Models & Mechanisms·Anni K SaralahtiMika Rämet
Apr 6, 2021·Genetics and Molecular Biology·Alex I KannoLuciana C C Leite
May 7, 2021·Immunological Reviews·Asma AhmedAnnapurna Vyakarnam
Jul 6, 2021·Expert Review of Vaccines·Lazaro M Marques-NetoLuciana C C Leite

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Methods Mentioned

BETA
PCR
Enzyme-linked immunosorbent assay

Software Mentioned

FlowJo

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