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2030-01-01
Sustainable Development Goals
03 Saúde e Bem-EstarCollections
- IOC - Artigos de Periódicos [12776]
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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
Author
Affilliation
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Health Protection Agency Centre for Emergency Preparedness and Response. Salisbury, UK.
Institut Pasteur. Unité de Régulation Immunitaire et Vaccinologie. Institut National de la Santé et de la Recherche Médicale. Paris, France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Fundação Ataulpho de Paiva. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Unité de Régulation Immunitaire et Vaccinologie. Institut National de la Santé et de la Recherche Médicale. Paris, France.
University of London. St George’s Vaccine Institut. London, UK.
Health Protection Agency Centre for Emergency Preparedness and Response. Salisbury, UK.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Health Protection Agency Centre for Emergency Preparedness and Response. Salisbury, UK.
Institut Pasteur. Unité de Régulation Immunitaire et Vaccinologie. Institut National de la Santé et de la Recherche Médicale. Paris, France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil / Fundação Ataulpho de Paiva. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Unité de Régulation Immunitaire et Vaccinologie. Institut National de la Santé et de la Recherche Médicale. Paris, France.
University of London. St George’s Vaccine Institut. London, UK.
Health Protection Agency Centre for Emergency Preparedness and Response. Salisbury, UK.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
Institut Pasteur. Unité de Génétique Mycobactérienne. Paris. France.
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.
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