Mycobacterium tuberculosis proteins involved in cell wall lipid biosynthesis improve BCG vaccine efficacy in a murine TB model

Int J Infect Dis. 2017 Mar;56:274-282. doi: 10.1016/j.ijid.2017.01.024. Epub 2017 Feb 2.

Abstract

Objectives: Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant.

Methods: Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later. Immune responses were examined at given time points. 9 weeks post vaccination, mice were aerosol-challenged with M. tb, and sacrificed at 6 and 12 weeks to assess bacterial burden.

Results: Vaccination of mice with BCG and M. tb proteins in the presence of GLA-SE adjuvant triggered strong IFN-γ and IL-2 production by splenocytes; more TNF-α was produced without GLA-SE addition. Antibody responses to all three antigens did not differ, with or without GLA-SE adjuvant. Protein boosting without GLA-SE adjuvant resulted in vaccinated animals having better control of pulmonary M. tb load at 6 and 12 weeks post aerosol infection, while animals receiving the protein boost with GLA-SE adjuvant exhibited more bacteria in the lungs.

Conclusions: Our data provides evidence for developing Rv2958c, Rv2957 and Rv0447c in a heterologous prime-boost vaccination strategy with BCG.

Keywords: Bacille Calmette-Guérin; Mycobacterium tuberculosis; T cells; antibodies; antigens; tuberculosis; vaccines.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antigens, Bacterial / immunology
  • BCG Vaccine / immunology*
  • Bacterial Proteins / immunology*
  • Cell Wall / metabolism*
  • Humans
  • Lipids / biosynthesis*
  • Mice
  • Mycobacterium tuberculosis* / immunology
  • Tuberculosis, Pulmonary / prevention & control
  • Vaccine Potency

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • Lipids