Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20822-7. doi: 10.1073/pnas.0806244105. Epub 2008 Dec 15.

Abstract

Respiratory syncytial virus (RSV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, because of an inefficient immunological memory, RSV infection provides limited immune protection against reinfection. Furthermore, RSV can induce an inadequate Th2-type immune response that causes severe respiratory tract inflammation and obstruction. It is thought that effective RSV clearance requires the induction of balanced Th1-type immunity, involving the activation of IFN-gamma-secreting cytotoxic T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which has been used in newborns for decades in several countries as a tuberculosis vaccine. Here, we show that immunization with recombinant BCG strains expressing RSV antigens promotes protective Th1-type immunity against RSV in mice. Activation of RSV-specific T cells producing IFN-gamma and IL-2 was efficiently obtained after immunization with recombinant BCG. This type of T cell immunity was protective against RSV challenge and caused a significant reduction of inflammatory cell infiltration in the airways. Furthermore, mice immunized with recombinant BCG showed no weight loss and reduced lung viral loads. These data strongly support recombinant BCG as an efficient vaccine against RSV because of its capacity to promote protective Th1 immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Immunity, Cellular
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / immunology*
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus Vaccines / pharmacology
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Th1 Cells / immunology*
  • Viral Load

Substances

  • Antigens, Viral
  • Interleukin-2
  • Respiratory Syncytial Virus Vaccines
  • Interferon-gamma