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Clinical Trial
. 2015 Aug 7;33(33):4130-40.
doi: 10.1016/j.vaccine.2015.06.051. Epub 2015 Jun 19.

First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Angelique Kany Kany Luabeya  1 , Benjamin M N Kagina  2 , Michele D Tameris  3 , Hennie Geldenhuys  3 , Soren T Hoff  4 , Zhongkai Shi  5 , Ingrid Kromann  4 , Mark Hatherill  3 , Hassan Mahomed  6 , Willem A Hanekom  3 , Peter Andersen  4 , Thomas J Scriba  3 ; H56-032 Trial Study Group; Elisma Schoeman  3 , Colleen Krohn  3 , Cheryl L Day  7 , Hadn Africa  3 , Lebohang Makhethe  3 , Erica Smit  3 , Yolande Brown  3 , Sara Suliman  3 , E Jane Hughes  3 , Peter Bang  4 , Margaret A Snowden  5 , Bruce McClain  5 , Gregory D Hussey  2
Affiliations
Clinical Trial

First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Angelique Kany Kany Luabeya et al. Vaccine. .

Abstract

Background: 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 Mycobacterium tuberculosis (M.tb) infection.

Methods: 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.

Results: 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(+) T cells. M.tb-infected vaccinees had higher frequencies of H56-induced CD4(+) T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ(+)TNF-α(+)IL-2(+)) and higher frequencies of H56-specific CD4(+) T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4(+) T cells, displaying a CD45RA(-)CCR7(-) effector memory phenotype, emerged after the second high-dose vaccination in M.tb-infected vaccinees. TNF-α(+)IL-2(+) H56-specific memory CD4(+) T cells were detected mostly after low-dose H56 vaccination in M.tb-infected vaccinees, and predominantly expressed a CD45RA(-)CCR7(+) central memory phenotype. Our results support further clinical testing of H56:IC31.

Keywords: Clinical trial; H56; Latent; Tuberculosis; Vaccine.

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