Safety and immunogenicity of candidate vaccine M72/AS01(E) in adolescents in a TB endemic setting

• Type of Material: Article
• Authors: Adam Penn-Nicholson, University of Cape Town; Hennie Geldenhuys, University of Cape Town; Wivine Burny, GSK Vaccines; Robbert van der Most, GSK Vaccines; Cheryl Liane Day, Emory University; Erik Jongert, GSK Vaccines; Philippe Moris, GSK Vaccines; Mark Hatherill, University of Cape Town; Opokua Ofori-Anyinam, GSK Vaccines; Willem Hanekom, University of Cape Town; Anna Bollaerts, GSK Vaccines; Marie-Ange Demoitie, GSK Vaccines; Angelique Kany Kany Luabeya, University of Cape Town; Evi De Ruymaeker, GSK Vaccines; Michele Tameris, University of Cape Town; Didier Lapierre, GSK Vaccines; Thomas J. Scriba, University of Cape Town
• Language: English
• Date: 2015-07-31
• Publisher: Elsevier: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Authors. Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2015.05.088
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 33
• Issue: 32
• Start Page: 4025
• End Page: 4034
• Grant/Funding Information: This work was supported by co-funding from Glaxo-SmithKline Biologicals S.A. and AERAS.; A.P.-N. is supported in part by The Carnegie Corporation of New York and The Claude Leon Foundation.; GlaxoSmithKline Biologicals S.A., as sponsor of the study, was involved in all stages of the study conduct and analysis.
• Keywords: MYCOBACTERIUM-TUBERCULOSIS INFECTION; Vaccine; CORRELATE; BCG VACCINATION; Medicine, Research & Experimental; Life Sciences & Biomedicine; CHILDREN; NK CELLS; Immunology; T cell; POLYFUNCTIONAL CD4(+); Research & Experimental Medicine; PROTECTION; NEGATIVE ADULTS; CELL RESPONSES; Tuberculosis; NK cell; PPD-POSITIVE ADULTS; M72/AS01(E); Cytokine; Science & Technology
• Research Categories: Health Sciences, General; Health Sciences, Immunology

Abstract

Background: Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01 E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. Methods: In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01 E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. Results: No serious adverse events were recorded. M72/AS01 E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. Conclusions: The clinically acceptable safety and immunogenicity profile of M72/AS01 E in adolescents living in an area with high TB burden support the move to efficacy trials.