Molecular characterization of heterologous HIV-1gp120 gene expression disruption in mycobacterium bovis BCG host strain: a critical issue for engineering mycobacterial based-vaccine vectors

J Biomed Biotechnol. 2010:2010:357370. doi: 10.1155/2010/357370. Epub 2010 Jun 27.

Abstract

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261) and Mycobacteria spp. alpha-antigen promoter (in plasmid pJH222). Among 14 rBCG:HIV-1gp120 (pMV261) colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222) colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines
  • Amino Acid Sequence
  • BCG Vaccine
  • Base Sequence
  • Blotting, Western
  • Gene Deletion
  • Gene Expression
  • Genetic Vectors / genetics*
  • HIV Envelope Protein gp120* / chemistry
  • HIV Envelope Protein gp120* / genetics
  • HIV Envelope Protein gp120* / metabolism
  • Molecular Sequence Data
  • Mycobacterium bovis / genetics*
  • Mycobacterium bovis / metabolism
  • Polymerase Chain Reaction
  • Transformation, Bacterial
  • Vaccines, Synthetic*

Substances

  • AIDS Vaccines
  • BCG Vaccine
  • HIV Envelope Protein gp120
  • Vaccines, Synthetic
  • gp120 protein, Human immunodeficiency virus 1