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

Vaccine. 2013 Feb 18;31(9):1340-8. doi: 10.1016/j.vaccine.2012.12.053. Epub 2013 Jan 3.

Abstract

Background: 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).

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 ΔureC::hly Hm(R)) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) 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-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.

Conclusions: VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / adverse effects*
  • BCG Vaccine / genetics
  • BCG Vaccine / immunology*
  • Flow Cytometry
  • Healthy Volunteers
  • Humans
  • Injections, Intradermal
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Young Adult

Substances

  • Antibodies, Bacterial
  • BCG Vaccine
  • Vaccines, Synthetic
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00749034