Subcutaneous boosting with heparin binding haemagglutinin increases BCG-induced protection against tuberculosis

Microbes Infect. 2009 Nov;11(13):995-1001. doi: 10.1016/j.micinf.2009.07.005. Epub 2009 Jul 25.


Pulmonary tuberculosis remains a major health problem. Effective vaccination strategies are urgently needed. It was previously demonstrated that purified Mycobacterium bovis BCG Heparin Binding Haemagglutinin (HBHA) is able to induce in BALB/c mice protection levels against a Mycobacterium tuberculosis infection that are similar to those offered by BCG. Here we developed a heterologous prime/boost immunisation approach using a combination of BCG and HBHA in order to increase the protective immune response. We show that the time period between BCG priming and HBHA boosting strongly influences the efficacy of the boost. The optimized vaccine protocol consisting of a BCG administration followed 8 months later by boosting with HBHA resulted in an increase in the level of protection of up to 0.7log when compared to BCG alone. These results suggest an immunisation strategy where BCG is administered to neonates and is followed by subcutaneous HBHA boosting in young adults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / pharmacology
  • Cells, Cultured
  • Disease Models, Animal
  • Drug Administration Schedule
  • Female
  • Immunization, Secondary*
  • Interferon-gamma / metabolism
  • Interleukin-5 / metabolism
  • Membrane Proteins / immunology*
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis / immunology*
  • Spleen / cytology
  • Statistics, Nonparametric
  • Tuberculosis / immunology
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / immunology
  • Tuberculosis Vaccines / pharmacology*


  • Bacterial Proteins
  • HbhA protein, Mycobacterium tuberculosis
  • Interleukin-5
  • Membrane Proteins
  • Tuberculosis Vaccines
  • Interferon-gamma