Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study
Journal
Tuberculosis
Journal Volume
100
Pages
118-127
Date Issued
2016
Author(s)
Gillard P.
Danilovits M.
Su W.-J.
Cheng S.-L.
Pehme L.
Bollaerts A.
Jongert E.
Moris P.
Ofori-Anyinam O.
Demoitié M.-A.
Castro M.
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-na?ve 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 ? 2016 GlaxoSmithKline Biologicals SA
Subjects
Immunogenicity; M72/AS01E vaccine; Safety; T-cell; Tuberculosis
SDGs
Other Subjects
aminotransferase; BCG vaccine; bilirubin; CD40 ligand; gamma interferon; interleukin 13; interleukin 17; interleukin 2; m72 as01e vaccine; placebo; tumor necrosis factor alpha; unclassified drug; bacterium antibody; BCG vaccine; adult; adult disease; aminotransferase blood level; Article; BCG vaccination; bilirubin blood level; CD4+ T lymphocyte; controlled study; drug safety; fatigue; female; fever; flow cytometry; follow up; headache; human; humoral immunity; immune response; immunogenicity; incidence; injection site reaction; injection site redness; injection site swelling; major clinical study; malaise; male; myalgia; pain; phase 2 clinical trial; priority journal; randomized controlled trial; side effect; single blind procedure; tuberculosis; adolescent; biosynthesis; cellular immunity; clinical trial; erythema; immunology; middle aged; multicenter study; Mycobacterium tuberculosis; pain; tuberculosis; young adult; Adolescent; Adult; Antibodies, Bacterial; CD4-Positive T-Lymphocytes; Erythema; Female; Humans; Immunity, Cellular; Male; Middle Aged; Mycobacterium tuberculosis; Pain; Single-Blind Method; Tuberculosis; Tuberculosis Vaccines; Young Adult
Publisher
Churchill Livingstone
Type
journal article