Prime-boost vaccination with rBCG/rAd35 enhances CD8⺠cytolytic T-cell responses in lesions from Mycobacterium tuberculosis-infected primates.
Mol Med
; 18: 647-58, 2012 May 09.
Article
em En
| MEDLINE
| ID: mdl-22396020
ABSTRACT
To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I-restricted CD8⺠cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens. Here, the capacity of the rBCG/rAd35 vaccine to induce protective and biologically relevant CD8⺠T-cell responses in a nonhuman primate model of TB was investigated. After prime/boost immunizations and challenge with virulent Mtb in rhesus macaques, quantification of immune responses at the single-cell level in cryopreserved tissue specimen from infected organs was performed using in situ computerized image analysis as a technological platform. Significantly elevated levels of CD3⺠and CD8⺠T cells as well as cells expressing interleukin (IL)-7, perforin and granulysin were found in TB lung lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35-vaccinated or unvaccinated animals. The local increase in CD8⺠cytolytic T cells correlated with reduced expression of the Mtb antigen MPT64 and also with prolonged survival after the challenge. Our observations suggest that a protective immune response in rBCG/rAd35-vaccinated nonhuman primates was associated with enhanced MHC class I antigen presentation and activation of CD8⺠effector T-cell responses at the local site of infection in Mtb-challenged animals.
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Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Vacina BCG
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Linfócitos T Citotóxicos
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Mycobacterium tuberculosis
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article