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.
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