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A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity
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A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity
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Journal Article
A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity
2012
Overview
► AERAS-402 boosts BCG immunity. ► AERAS-402 induces higher levels of CD8+ T cells than other TB vaccines. ► AERAS-402 induces polyfunctional CD4++CD8+ T cells.
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.
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.
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.
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.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Acyltransferases - immunology
/ Adenoviruses, Human - genetics
/ Adult
/ antigens
/ Antigens, Bacterial - genetics
/ Antigens, Bacterial - immunology
/ Bacterial Proteins - genetics
/ Bacterial Proteins - immunology
/ BCG
/ CD4-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Humans
/ Immunity
/ Mycobacterium tuberculosis - genetics
/ Mycobacterium tuberculosis - immunology
/ Peptides
/ Tuberculosis Vaccines - administration & dosage
/ Tuberculosis Vaccines - genetics
/ Tuberculosis Vaccines - immunology
/ Vaccines
