title: Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.
abstract: 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.
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: paul.gillard@gsk.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.affiliation: National Taiwan University Hospital, 7 Chung-Shan South Road, 10002 Taipei, Taiwan.
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.affiliation: Lung Clinic of Tartu University Hospital, 167 Riia St., 51014 Tartu, Estonia.
authors.forename: Manfred
authors.initials: M
authors.lastname: Danilovits
authors.affiliation: Taipei Veterans General Hospital and National Yang-Ming University, No 201, Sec. 2, Shipai Rd, 11217 Taipei, Taiwan.
authors.forename: Wei-Juin
authors.initials: WJ
authors.lastname: Su
authors.affiliation: Far Eastern Memorial Hospital, No. 122-23, Sec. 2, Nanya S Rd, 220 New Taipei City, Taiwan.
authors.forename: Shih-Lung
authors.initials: SL
authors.lastname: Cheng
authors.affiliation: Lung Clinic of Tartu University Hospital, 167 Riia St., 51014 Tartu, Estonia.
authors.forename: Lea
authors.initials: L
authors.lastname: Pehme
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bollaerts
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.affiliation: GSK Vaccines, Avenue Fleming 20, 1300 Wavre/Rue de l'Institut 89, 1330 Rixensart, Belgium.
authors.forename: Marcela
authors.initials: M
authors.lastname: Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004890:Erythema / Q000209:etiology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010146:Pain / Q000209:etiology; D016037:Single-Blind Method; D014376:Tuberculosis / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000009:adverse effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D032581:Tuberculosis Vaccines
keywords: Immunogenicity; M72/AS01(E) vaccine; Safety; T-cell; Tuberculosis