Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial

Background: Current vaccination using Mycobacterium bovis bacillus Calmette-Guerin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034). Methods: Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG Delta ureC::hly Hm(R)) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-gamma) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens. Results: Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naive, n=40 and BCG-immune, n = 40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-gamma-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naive and BCG-immune individuals. Conclusions: VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline. (C) 2012 Elsevier Ltd. All rights reserved.