Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting. Issue 32 (31st July 2015)

• Record Type: Journal Article
• 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.; the Vaccine Study Team
• Is Part Of: Vaccine. Volume 33:Issue 32(2015)
• Page Start: 4025
• Page End: 4034
• Publication Date: 2015-07-31
• Subjects: Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.05.088
• Languages: English
• ISSNs: 0264-410X

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">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<sub>E</sub> was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of <italic>Mycobacterium tuberculosis</italic> (<italic>M.tb</italic>) infection status.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">In a phase II, double-blind randomized, controlled study (<ext-link ext-link-type="unknown" id="intr0005" xlink:type="simple" xlink:href="ctgov:NCT00950612" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00950612</ext-link>), two doses of M72/AS01<sub>E</sub> 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.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">No serious adverse events were recorded. M72/AS01<sub>E</sub> 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 <italic>M.tb</italic> 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 <italic>M.tb</italic>-infected participants, suggesting natural infection acts as a prime to vaccination.</p> </sec> <sec> <title id="sect0025">Conclusions</title> <p id="spar0020">The clinically acceptable safety and immunogenicity profile of M72/AS01<sub>E</sub> in adolescents living in an area with high TB burden support the move to efficacy trials.</p> </sec> </abstract>