Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study. (September 2016)

• Record Type: Journal Article
• Authors: Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela
• Is Part Of: Tuberculosis. Volume 100(2016)
• Page Start: 118
• Page End: 127
• Publication Date: 2016-09
• Subjects: Tuberculosis -- M72/AS01E vaccine -- Safety -- Immunogenicity -- T-cell; AE adverse event -- ATP according to protocol -- BCG Bacille Calmette-Guérin -- CFP10 culture filtrate protein-10 -- CI confidence interval -- CMI cell-mediated immunity -- ELISA enzyme linked immunosorbent assay -- EU/mL ELISA units per millilitre -- GMC geometric mean concentration -- HIV human immunodeficiency virus -- ICS intracellular cytokine staining -- IFN-γ interferon-gamma -- IL interleukin -- MedDRA medical dictionary for regulatory activities -- PBMC peripheral blood mononuclear cell -- PPD purified protein derivative -- SAE serious adverse event -- SAS statistical analysis system -- TB tuberculosis -- TNF-α tumour necrosis factor-alpha -- TVC total vaccinated cohort; 616.995
• DOI: 10.1016/j.tube.2016.07.005
• Languages: English
• ISSNs: 1472-9792

Abstract

Summary: Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis -infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18–59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E -vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4 + T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov:NCT01424501