Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

• Published in: Vaccine 2015-07, Vol.33 (32), p.4025-4034
• Main Authors: Penn-Nicholson, Adam, Geldenhuys, Hennie, Burny, Wivine, van der Most, Robbert, Day, Cheryl L, Jongert, Erik, Moris, Philippe, Hatherill, Mark, Ofori-Anyinam, Opokua, Hanekom, Willem, Bollaerts, Anne, Demoitie, Marie-Ange, Kany Luabeya, Angelique Kany, De Ruymaeker, Evi, Tameris, Michele, Lapierre, Didier, Scriba, Thomas J
• Format: Article
• Language: English
• Subjects: Adolescent; Allergy and Immunology; Antigens, Bacterial - immunology; Cytokine; Cytokines - biosynthesis; Double-Blind Method; Drug Combinations; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Endemic Diseases; Female; Flow Cytometry; Human immunodeficiency virus; Humans; Injections, Intramuscular; Killer Cells, Natural - immunology; Lipid A - administration & dosage; Lipid A - adverse effects; Lipid A - analogs & derivatives; M72/AS01E; Male; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; NK cell; Placebos - administration & dosage; Saponins - administration & dosage; Saponins - adverse effects; Staining and Labeling; T cell; T-Lymphocytes - immunology; Treatment Outcome; Tuberculosis; Tuberculosis - epidemiology; Tuberculosis - prevention & control; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - adverse effects; Tuberculosis Vaccines - immunology; Vaccine; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - adverse effects; Vaccines, Subunit - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2015.05.088

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/AS01E 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/AS01E 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/AS01E 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/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials.