Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants

J Infect Dis. 2011 Jun 15;203(12):1832-43. doi: 10.1093/infdis/jir195.


Background: BCG, the only licensed tuberculosis vaccine, affords poor protection against lung tuberculosis in infants and children. A new tuberculosis vaccine, which may enhance the BCG-induced immune response, is urgently needed. We assessed the safety of and characterized the T cell response induced by 3 doses of the candidate vaccine, MVA85A, in BCG-vaccinated infants from a setting where tuberculosis is endemic.

Methods: Infants aged 5-12 months were vaccinated intradermally with either 2.5 × 10(7), 5 × 10(7), or 10 × 10(7) plaque-forming units of MVA85A, or placebo. Adverse events were documented, and T-cell responses were assessed by interferon γ (IFN-γ) enzyme-linked immunospot assay and intracellular cytokine staining.

Results: The 3 MVA85A doses were well tolerated, and no vaccine-related serious adverse events were recorded. MVA85A induced potent, durable T-cell responses, which exceeded prevaccination responses up to 168 d after vaccination. No dose-related differences in response magnitude were observed. Multiple CD4 T cell subsets were induced; polyfunctional CD4 T cells co-expressing T-helper cell 1 cytokines with or without granulocyte-macrophage colony-stimulating factor predominated. IFN-γ-expressing CD8 T cells, which peaked later than CD4 T cells, were also detectable.

Conclusions: MVA85A was safe and induced robust, polyfunctional, durable CD4 and CD8 T-cell responses in infants. These data support efficacy evaluation of MVA85A to prevent tuberculosis in infancy. Clinical Trials Registration. NCT00679159.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / immunology
  • Age Factors
  • Antigens, Bacterial / immunology
  • BCG Vaccine / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Infant
  • Interferon-gamma / metabolism
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Placebos
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / administration & dosage
  • Tuberculosis Vaccines / adverse effects
  • Tuberculosis Vaccines / immunology*
  • Tuberculosis Vaccines / standards


  • Antigens, Bacterial
  • BCG Vaccine
  • Placebos
  • Tuberculosis Vaccines
  • Interferon-gamma
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis

Associated data