Browsing by Author "Mahomed, Hassan"

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    First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
    (Vaccine, 2015) Luabeya, Angelique Kany Kany; Kagina, Benjamin M.N.; Kromann, Ingrid; Mahomed, Hassan; Hanekom, Willem A.
    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. Low dose (15μg H56 protein in 500nmol IC31) or high dose (50μg H56, 500nmol 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. 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.
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    Higher human CD4 T cell response to novel Mycobacterium Tuberculosis Latency associated Antigens Rv2660 and Rv2659 in Latent Infection compared with Tuberculosis Disease
    (Vaccine, 2010) Govender, Lerisa; Scriba, Thomas J.; Kagina, Benjamin M.N.; Rosenkrands, Ida; Mahomed, Hassan
    One third of the world's population is infected with Mycobacterium tuberculosis (M.tb). A vaccine that would prevent progression to TB disease will have a dramatic impact on the global TB burden. We propose that antigens of M.tb that are preferentially expressed during latent infection will be excellent candidates for post-exposure vaccination. We therefore assessed human T cell recognition of two such antigens, Rv2660 and Rv2659. Expression of these was shown to be associated with non-replicating persistence in vitro. After six days incubation of PBMC from persons with latent tuberculosis infection (LTBI) and tuberculosis (TB) disease, Rv2660 and Rv2659 induced IFN-γ production in a greater proportion of persons with LTBI, compared with TB diseased patients. Persons with LTBI also had increased numbers of viable T cells, and greater specific CD4+ T cell proliferation and cytokine expression capacity. Persons with LTBI preferentially recognize Rv2659 and Rv2660, compared with patients with TB disease. These results suggest promise of these antigens for incorporation into post-exposure TB vaccines.