Abstract
BackgroundNovel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults.MethodsHIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5∶1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.Results47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.ConclusionH1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.Trial registrationPan African Clinical Trials Registry (PACTR) PACTR201105000289276
Highlights
Tuberculosis (TB) remains a global public health problem
[4] In this phase II trial we evaluated the safety and immunogenicity of Hybrid 1 (H1)/IC31administered to HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3 and without evidence of active TB disease (PACTR Identifier: PACTR201105000289276)
There was no difference in IgG levels by study arms two week post second vaccination and 182. This is the first report on safety and immunogenicity of the H1/IC31 subunit TB vaccine administered to HIV-infected adults with CD4+ lymphocyte counts .350 cells/mm3
Summary
Tuberculosis (TB) remains a global public health problem. One third of humankind is infected with Mycobacterium tuberculosis (M.tb), which according to the World Health Organization (WHO) led to almost 8.6 million new active TB cases and 1.3 million TB deaths in 2012 [1]. Mycobacterium bovis Bacille CalmetteGuerin (BCG), the only currently licensed TB vaccine, is effective in preventing severe progressive disease in children but has limited impact on adult pulmonary TB, the driving force of the TB global pandemic [2] [3]. The Statens Serum Institut Hybrid (H1) recombinant fusion protein (antigen (Ag)85B- Early Secretory Antigenic Target (ESAT)-6) TB vaccine, adjuvanted with IC31, has been shown to be safe and immunogenic in BCG unvaccinated, TB uninfected participants and in BCG vaccinated and latently TB infected participants [4] In this phase II trial we evaluated the safety and immunogenicity of H1/IC31administered to HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm and without evidence of active TB disease (PACTR Identifier: PACTR201105000289276)
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