First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Issue 33 (7th August 2015)

• Record Type: Journal Article
• Authors: Luabeya, Angelique Kany Kany; Kagina, Benjamin M.N.; Tameris, Michele D.; Geldenhuys, Hennie; Hoff, Soren T.; Shi, Zhongkai; Kromann, Ingrid; Hatherill, Mark; Mahomed, Hassan; Hanekom, Willem A.; Andersen, Peter; Scriba, Thomas J.; H56-032 Trial Study Group, 1; Schoeman, Elisma; Krohn, Colleen; Day, Cheryl L.; Africa, Hadn; Makhethe, Lebohang; Smit, Erica; Brown, Yolande; Suliman, Sara; Hughes, E. Jane; Bang, Peter; Snowden, Margaret A.; McClain, Bruce; Hussey, Gregory D.
• Is Part Of: Vaccine. Volume 33:Issue 33(2015)
• Page Start: 4130
• Page End: 4140
• Publication Date: 2015-08-07
• Subjects: Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.06.051
• 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">H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with <italic>Mycobacterium tuberculosis</italic> (<italic>M.tb</italic>) infection.</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">Low dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4<sup>+</sup> T cells. <italic>M.tb</italic>-infected vaccinees had higher frequencies of H56-induced CD4<sup>+</sup> T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ<sup>+</sup>TNF-α<sup>+</sup>IL-2<sup>+</sup>) and higher frequencies of H56-specific CD4<sup>+</sup> T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4<sup>+</sup> T cells, displaying a CD45RA<sup>−</sup>CCR7<sup>−</sup> effector memory phenotype, emerged after the second high-dose vaccination in <italic>M.tb</italic>-infected vaccinees. TNF-α<sup>+</sup>IL-2<sup>+</sup> H56-specific memory CD4<sup>+</sup> T cells were detected mostly after low-dose H56 vaccination in <italic>M.tb</italic>-infected vaccinees, and predominantly expressed a CD45RA<sup>−</sup>CCR7<sup>+</sup> central memory phenotype. Our results support further clinical testing of H56:IC31.</p> </sec> </abstract>