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

• Published in: Vaccine Vol. 31; no. 9; pp. 1340 - 1348
• Main Authors: Grode, Leander, Ganoza, Christian A., Brohm, Christiane, Weiner, January, Eisele, Bernd, Kaufmann, Stefan H.E.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 18.02.2013; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Allergy and Immunology; antibodies; Antibodies, Bacterial - blood; Antigens; Applied microbiology; B-lymphocytes; bacterial antigens; BCG; BCG vaccine; BCG Vaccine - administration & dosage; BCG Vaccine - adverse effects; BCG Vaccine - genetics; BCG Vaccine - immunology; Biological activity; Biological and medical sciences; blood serum; cell-mediated immunity; Clinical trial; Clinical trials; Cytokines; Enzymes; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Genetic engineering; Healthy Volunteers; Humans; Immune response; Immunogenicity; Injections, Intradermal; interferon-gamma; Interferon-gamma - secretion; Leukocytes, Mononuclear - immunology; Male; Microbiology; Middle Aged; Mycobacterium bovis; Mycobacterium bovis BCG; randomized clinical trials; Safety; Skin; T-lymphocytes; Tuberculosis; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; volunteers; Young Adult; Clinical trial; Tuberculosis; Immune response; Safety; Vaccination; BCG; Immunogenicity; Vaccine
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2012.12.053

► The recombinant BCG vaccine VPM1002 was tested in PPD+ and PPD− individuals. ► VPM1002 successfully completed a phase I clinical trial. ► VPM1002 was as safe as BCG. ► VPM1002 and BCG induced both shared and differential immune responses. Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (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). 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 ΔureC::hly HmR) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens. Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, 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-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals. VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline.