A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity.
Vaccine
; 30(12): 2098-108, 2012 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-22296955
ABSTRACT
BACKGROUND:
Despite the availability of Bacille Calmette Guérin (BCG) vaccines, Mycobacterium tuberculosis currently infects billions of people and millions die annually from tuberculosis (TB) disease. New TB vaccines are urgently needed.METHODS:
We studied the ability of AERAS-402, a recombinant, replication-deficient adenovirus type 35 expressing the protective M. tuberculosis antigens Ag85A, Ag85B, and TB10.4, to boost BCG immunity in an area of low TB endemicity.RESULTS:
In volunteers primed with BCG 3 or 6 months prior to AERAS-402 boosting, significant CD4(+) and CD8(+) T cell responses were induced. Ag85-specific responses were more strongly boosted than TB10.4-specific responses. Frequencies of TB-specific CD8(+) T cells reached>50 fold higher than pre-AERAS boosting levels, remarkably higher than reported in any previous human TB vaccine trial. Multiparameter flow cytometric assays demonstrated that AERAS-402-boosted CD4(+) and CD8(+) T cells were multifunctional, producing multiple cytokines and other immune effector molecules. Furthermore, boosted T cells displayed lymphoproliferative capacity, and tetramer analyses confirmed that antigen-specific CD8(+) T cells were induced. BCG and AERAS-402 vaccinations given 3 and 6 months apart appeared equivalent.CONCLUSIONS:
Our results indicate that AERAS-402 is a promising TB vaccine candidate that can significantly enhance both CD4(+) and CD8(+) TB-specific T cell responses after BCG priming. ClinicalTrials.gov Identifier NCT01378312.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Aciltransferases
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Adenovírus Humanos
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Vacinas contra a Tuberculose
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Vetores Genéticos
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Mycobacterium tuberculosis
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Antígenos de Bactérias
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article