First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults |
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| Affiliation: | 1. South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM), School of Child and Adolescent Health, University of Cape Town, University of Cape Town, Cape Town, South Africa;2. Vaccines for Africa Initiative, Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa;3. Statens Serum Institut (SSI), Copenhagen, Denmark;4. Aeras, Rockville, MD, USA;5. Western Cape Government and Stellenbosch University, Cape Town, South Africa;1. South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM), School of Child and Adolescent Health, University of Cape Town, University of Cape Town, Cape Town, South Africa;2. Vaccines for Africa Initiative, Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa;3. Statens Serum Institut (SSI), Copenhagen, Denmark;4. Aeras, Rockville, MD, USA;6. Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA;7. Emory Vaccine Center, Emory University, Atlanta, GA, USA;1. Aurum Institute, Johannesburg, South Africa;2. School of Public Health, University of Witwatersrand, Johannesburg, South Africa;3. Aeras, Rockville, MD, United States;4. Crucell Holland N.V., Leiden, The Netherlands;1. Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;2. Vaccination and Immunotherapy Centre, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;3. Department of Microbiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;4. Clinical Research Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;5. Service de Médecine du Personnel, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;6. Biofabri, Porriño, Spain;7. Department of Microbiology, Faculty of Medicine, University of Zaragoza, Spain;8. CIBERES and Research Network on Respiratory Diseases, Spanish Ministry of Health and Instituto de Salud Carlos III, Madrid, Spain;9. Servicio de Microbiología, Hospital Miguel Servet, ISS Aragón, Zaragoza, Spain;1. South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa;2. Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands;3. Aeras, Rockville, MD, USA;4. United States Army Medical Research Institute of Infectious Diseases, Washington, DC, USA;5. South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa;6. Vaccines for Africa Initiative, Division of Medical Microbiology & Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa;7. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore;8. Western Cape Government and Stellenbosch University, Cape Town, South Africa;9. Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands;10. Bill and Melinda Gates Foundation, Seattle, WA, USA;1. Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;2. Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102, USA;1. South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa;2. GSK Vaccines, Rixensart, Belgium;3. Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA;4. Emory Vaccine Center, Emory University, Atlanta, GA, USA;1. South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa;2. GSK Vaccines, Rixensart, Belgium |
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| Abstract: | BackgroundH56: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.MethodsLow 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.ResultsOne 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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| Keywords: | Tuberculosis Vaccine H56 Latent Clinical trial |
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