Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity.

Abstract

We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting of the mucosal adjuvant LTK63 and the Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette-Guérin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A. Because a crucial element of novel vaccine strategies is the ability to boost BCG-derived immunity, we also tested whether LTK63/Ag85B-ESAT-6 could act as a BCG booster vaccine in BCG-vaccinated mice. We found that vaccinating with LTK63/Ag85B-ESAT-6 strongly boosted prior BCG-stimulated immunity. Compared with BCG-vaccinated nonboosted mice, we observed that infection with M.tb led to a significant increase in anti-M.tb-specific CD4 T cells in the lungs of LTK63/Ag85B-ESAT-6-boosted animals. This correlated with a significant increase in the protection against M.tb in LTK63/Ag85B-ESAT-6-boosted mice, compared with BCG-vaccinated animals. Thus, LTK63/Ag85B-ESAT-6 represents an efficient preventive vaccine against tuberculosis with a strong ability to boost prior BCG immunity.

• Authors: Jes Dietrich, Claire Andersen, Rino Rappuoli, T Mark Doherty, Charlotte Green Jensen, Peter Andersen
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 9 Pg. 6353-60 (Nov 01 2006) ISSN: 0022-1767 [Print] United States
• PMID: 17056566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• Bacterial Toxins
• ESAT-6 protein, Mycobacterium tuberculosis
• Enterotoxins
• Escherichia coli Proteins
• Recombinant Fusion Proteins
• Tuberculosis Vaccines
• heat-labile enterotoxin, E coli
• Acyltransferases
• antigen 85B, Mycobacterium tuberculosis

Topics

• Acyltransferases (administration & dosage, immunology)
• Administration, Intranasal
• Animals
• Antigens, Bacterial (administration & dosage, immunology)
• Bacterial Proteins (administration & dosage, immunology)
• Bacterial Toxins (administration & dosage, immunology)
• Enterotoxins (administration & dosage, immunology)
• Escherichia coli Proteins (administration & dosage, immunology)
• Immunization, Secondary
• Mice
• Mice, Inbred Strains
• Mycobacterium bovis (immunology)
• Mycobacterium tuberculosis
• Nasal Mucosa (immunology)
• Recombinant Fusion Proteins (administration & dosage, immunology)
• T-Lymphocytes (immunology)
• Tuberculosis Vaccines (administration & dosage, immunology, therapeutic use)
• Tuberculosis, Pulmonary (prevention & control)
• Vaccination