We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Prime-Boost Vaccination with rBCG/rAd35 Enhances CD8<sup>+</sup> Cytolytic T-Cell Responses in Lesions from Mycobacterium Tuberculosis - Infected Primates.
- Authors
Rahman, Sayma; Magalhaes, Isabelle; Rahman, Jubayer; Ahmed, Raija K.; Sizemore, Donata R.; Scanga, Charles A.; Weichold, Frank; Verreck, Frank; Kondova, Ivanela; Sadoff, Jerry; Thorstensson, Rigmor; Spångberg, Mats; Svensson, Mattias; Andersson, Jan; Maeurer, Markus; Brighenti, Susanna
- 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+ 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+ 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+ and CD8+ 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+ 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+ effector T-cell responses at the local site of infection in Mtb-challenged animals.
- Subjects
VACCINATION; TUBERCULOSIS; T cells; MAJOR histocompatibility complex; ANTIGENS
- Publication
Molecular Medicine, 2012, Vol 18, Issue 4, p647
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/molmed.2011.00222