PLoS ONE (Jan 2012)

Vaccination with a BCG strain overexpressing Ag85B protects cattle against Mycobacterium bovis challenge.

  • Caroline Rizzi,
  • María Verónica Bianco,
  • Federico Carlos Blanco,
  • Marcelo Soria,
  • María José Gravisaco,
  • Valeria Montenegro,
  • Lucas Vagnoni,
  • Bryce Buddle,
  • Sergio Garbaccio,
  • Fernando Delgado,
  • Karen Silva Leal,
  • Angel Adrián Cataldi,
  • Odir Antônio Dellagostin,
  • Fabiana Bigi

DOI
https://doi.org/10.1371/journal.pone.0051396
Journal volume & issue
Vol. 7, no. 12
p. e51396

Abstract

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Mycobacterium bovis is the causative agent of tuberculosis in cattle but also infects other animals, including humans. Previous studies in cattle have demonstrated that the protection induced by BCG is not complete. In order to improve the protection efficacy of BCG, in this study we overexpressed Ag85B in a BCG Pasteur strain, by using an expression system based on the use of an auxotrophic strain for the leucine amino acid, and complementation with leuD. We found that vaccination of cattle with BCG overexpressing Ag85B induced higher production of IL-17 and IL-4 mRNA upon purified protein derivative (PPDB) stimulation of peripheral blood mononuclear cells (PBMCs) than vaccination with BCG. Moreover, the IL-17 mRNA expression after vaccination negatively correlated with disease severity resulting from a subsequent challenge with M. bovis, suggesting that this cytokine is a potential biomarker of cattle protection against bovine tuberculosis. Importantly, vaccination with the recombinant BCG vaccine protected cattle better than the wild-type BCG Pasteur.