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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-gamma producing T-cells.
- Source :
-
Vaccine [Vaccine] 2009 Jan 01; Vol. 27 (1), pp. 28-37. Date of Electronic Publication: 2008 Oct 31. - Publication Year :
- 2009
-
Abstract
- The potent IFN-gamma 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-gamma 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-gamma secretion by circulating T-cells, mucosal regimens induced barely detectable IFN-gamma. 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-gamma responses sharply increased in non-vaccinated mice as a hallmark of infection. Parenterally immunized mice that controlled Mtb infection, displayed anti-ESAT-6 IFN-gamma 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-gamma T-cell response remained low.
- Subjects :
- Administration, Intranasal
Animals
Female
Guinea Pigs
Humans
Immunization, Secondary
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mycobacterium bovis immunology
Mycobacterium tuberculosis immunology
Mycobacterium tuberculosis metabolism
Tuberculosis immunology
Acyltransferases immunology
Antigens, Bacterial immunology
BCG Vaccine administration & dosage
BCG Vaccine chemistry
BCG Vaccine immunology
Bacterial Proteins immunology
Interferon-gamma immunology
T-Lymphocytes immunology
Tuberculosis prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0264-410X
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 18977269
- Full Text :
- https://doi.org/10.1016/j.vaccine.2008.10.034