Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG.
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.
Bueno
Susan M
SM
Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.
González
Pablo A
PA
Cautivo
Kelly M
KM
Mora
Jorge E
JE
Leiva
Eduardo D
ED
Tobar
Hugo E
HE
Fennelly
Glenn J
GJ
Eugenin
Eliseo A
EA
Jacobs
William R
WR
Riedel
Claudia A
CA
Kalergis
Alexis M
AM
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D019562:Viral Load
D000956:Antigens, Viral; D007376:Interleukin-2; D022261:Respiratory Syncytial Virus Vaccines; D007371:Interferon-gamma