Protection against tuberculosis induced by oral prime with Mycobacterium bovis BCG and intranasal subunit boost based on the vaccine candidate Ag85B-ESAT-6 does not correlate with circulating IFN-γ producing T-cells

• Published in: Vaccine Vol. 27; no. 1; pp. 28 - 37
• Main Authors: Badell, Edgar, Nicolle, Fabienne, Clark, Simon, Majlessi, Laleh, Boudou, Frédéric, Martino, Angelo, Castello-Branco, Luiz, Leclerc, Claude, Lewis, David J.M., Marsh, Philip D., Gicquel, Brigitte, Winter, Nathalie
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.01.2009; Elsevier
• Subjects: Acyltransferases - immunology; Administration, Intranasal; Allergy and Immunology; Animals; Antigens, Bacterial - immunology; Applied microbiology; Bacterial diseases; Bacterial Proteins - immunology; Bacteriology; BCG Vaccine - administration & dosage; BCG Vaccine - chemistry; BCG Vaccine - immunology; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Human bacterial diseases; Humans; IFNγ; Immunization, Secondary; Infectious diseases; Interferon-gamma - immunology; Life Sciences; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Miscellaneous; Mucosa; Mycobacterium bovis - immunology; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - metabolism; T-Lymphocytes - immunology; Tuberculosis - immunology; Tuberculosis - prevention & control; Tuberculosis and atypical mycobacterial infections; Tuberculosis vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); IFNγ; Tuberculosis vaccines; Mucosa; Mycobacterium bovis; Cytokine; BCG; Vaccine; Intranasal administration; Mycobacterial infection; Subunit; Infection; Tuberculosis; Mycobacteriales; T-Lymphocyte; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes; Gamma interferon; MUCOSA; TUBERCULOSIS VACCINES; IFN GAMMA
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.10.034

The potent IFN-γ inducing fusion antigen Ag85B-ESAT-6 (85B6) is a lead subunit candidate to improve current vaccination against Mycobacterium tuberculosis (Mtb). The recombinant M. bovis BCG strain Myc3504 was constructed to secrete 85B6. It was based on commercial BCG strain Moreau Rio de Janeiro (BCG MoWT) which remains available for human oral administration. Myc 3504 induced higher levels of 85B6-specific IFN-γ circulating T-cells as compared to BCG MoWT. A novel needle-free mucosal immunization regimen combining oral prime with Myc3504 or BCG MoWT with intranasal boost with LTK-63-adjuvanted 85B6 was compared to subcutaneous prime-boost immunization. Strikingly whereas parenteral immunization induced sustained levels of 85B6-specific IFN-γ secretion by circulating T-cells, mucosal regimens induced barely detectable IFN-γ. Despite this, mice and guinea pigs immunized with the mucosal regimens were as efficiently protected against aerosol Mtb challenge as parenterally immunized animals. After Mtb challenge, anti-ESAT-6 IFN-γ responses sharply increased in non-vaccinated mice as a hallmark of infection. Parenterally immunized mice that controlled Mtb infection, displayed anti-ESAT-6 IFN-γ responses as high as non-immunized infected mice, compromising the possible use of ESAT-6 as a diagnostic tool. Interestingly, in mucosally immunized mice that were equally protected, post-challenge ESAT-6-specific IFN-γ T-cell response remained low.