• Richard N van Zyl-Smit, Aliasgar Esmail, Mary E Bateman, Rodney Dawson, Jonathan Goldin, Eva van Rikxoort, Macaya Douoguih, PauMaria GraziaMG4 Crucell Holland B.V., a Janssen Pharmaceutical company of Johnson & Johnson, Leiden, the Netherlands., Jerald C Sadoff, J Bruce McClain, Margaret Ann Snowden, Jacqueline Benko, David A Hokey, Kathryn Tucker Rutkowski, Andrew Graves, Barbara Shepherd, Sadritdin Ishmukhamedov, KaginaBenjamin M NBMN6 South African TB Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, and.7 Vaccines for Africa Initiative, Division of Medical Microbiology, Institute of Infec, Brian Abel, Willem A Hanekom, Thomas J Scriba, and Eric D Bateman.
• 1 University of Cape Town Lung Institute, Division of Pulmonology, Department of Medicine.
• Am. J. Respir. Crit. Care Med. 2017 May 1; 195 (9): 1171-1180.

RationaleAdministration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions.ObjectivesTo assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB.MethodsWe performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining.Measurements And Main ResultsNo apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups.ConclusionsAdministration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

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