Adenoviral-vectored tuberculosis vaccine AERAS-402 enhances T cell cytokine response in TB+ patients. (VAC12P.1026)

• Published in: The Journal of immunology (1950) Vol. 192; no. 1_Supplement; pp. 206 - 206.15
• Main Authors: Graves, Andrew, van Zyl-Smit, Richard, Esmail, Ali, Bateman, Mary, Dawson, Rodney, Goldin, Jonathan, van Rikxoort, Eva, Douoguih, Macaya, Pau, Maria, Sadoff, Jerald, Bennett, Sean, Snowden, Margaret, Gearhart, Jacqueline, Ishmukhamedov, Sadritdin, Schrager, Lewis, McClain, J., Bateman, Eric, Hokey, David
• Format: Journal Article
• Language: English
• Published: 01.05.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.206.15

Abstract Development of a vaccine to prevent pulmonary tuberculosis remains a public health priority. AERAS-402 is a live, replication-deficient adenovirus 35-vectored TB vaccine expressing the mycobacterial antigens 85A, 85B, and TB10.4. While this vaccine has been shown to be safe in TB uninfected patients, little is known about the performance of this vaccine in TB-experienced populations. The safety and immunogenicity of AERAS-402 was evaluated in a Phase 2a randomized, placebo-controlled, double-blinded dose-escalation study in HIV-negative South African adults with either active or recent pulmonary TB infection. Peripheral blood mononuclear cells isolated from trial patients were assessed via intracellular cytokine staining (ICS) examining T cells for interferon-γ (IFN-γ), TNF, and IL-2 production. While modest CD4+ T cell responses were observed, the ICS data indicate the induction of a robust, dominant CD8+ T cell response not observed in placebo patients, including instances of total cytokine responsive cells approaching 6% of CD8+ T cells in some subjects. Polyfunctional analysis revealed that vaccine-specific T cells were primarily secreting IFN-γ either alone or in combination with TNF following stimulation. These data suggest that AERAS-402 is able to boost T cell responses in patients with a history of TB infection.