Alteration of epitope recognition pattern in Ag85B and ESAT-6 has a profound influence on vaccine-induced protection against Mycobacterium tuberculosis

Eur J Immunol. 2006 Dec;36(12):3346-55. doi: 10.1002/eji.200636128.


To analyze the effect of vaccine delivery systems on antigen recognition and vaccine efficacy, we compared immune responses in mice immunized either with an adenovirus vector expressing a fusion of Ag85B and ESAT-6 or with the recombinant fusion protein in a liposomal adjuvant. Both vaccines induced high levels of antigen-specific IFN-gamma production. The adjuvanted protein vaccine induced primarily a CD4 T cell response directed to the epitope Ag85B(241-255) and gave efficient protection against subsequent Mycobacterium tuberculosis infection. In contrast, the adenoviral construct induced a strong CD8 response predominantly targeted to the epitope ESAT-6(15-29) and no significant protection against infection. Vaccination with the protein vaccine resulted in highly accelerated recall of Ag85B(241-255)-specific T cells immediately post M. tuberculosis challenge whereas the ESAT-6(15-29) epitope was barely recognized during infection. Delivery of the viral construct in cationic liposomes switched the immune response to a protective one dominated by CD4 T cells targeted to the Ag85B(241-255) epitope. These data demonstrate that the nature of the T cell response to a vaccine antigen is more important than its magnitude with respect to protective efficacy and that vaccine-mediated changes in immunodominance can result in T cell responses of limited relevance during the natural infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology*
  • Acyltransferases / metabolism
  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / metabolism
  • Cell Line
  • Epitope Mapping*
  • Female
  • Immunologic Memory / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / genetics
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology


  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Tuberculosis Vaccines
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis