Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice.
Viral DNA vaccines encoding the glycoprotein B (gB) of cytomegalovirus provide partial protective immunity upon challenge with infectious virus. Although it is known that type I IFN can stimulate the adaptive immune response, their direct use in vaccines has been limited. Here we show that coimmunisation of type I IFN and gB CMV DNA constructs enhances protective immunity in mice. In vivo expression of IFN transgenes ranged from 1.2 to 2.0 x 10(4) IU/g tibialis anterior muscle. Viral titre in major target organs and the severity of acute CMV-induced myocarditis was reduced preferentially with either IFN-alpha 9 or IFN-beta, but not with IFN-alpha 6, coimmunisation. However, all IFN subtypes investigated markedly reduced chronic myocarditis in gB-vaccinated mice. The early antiviral IgG1 and IgG2a titres were enhanced with IFN-beta coimmunisation. TNF and IL-10 was increased in response to MCMV infection in mice coimmunised with IFN subtypes and viral gB DNA. Indeed T cells from IFN-inoculated mice reduced myocarditis upon in vivo transfer. These results suggest that select type I IFNs may act as a natural adjuvant for the immune response against CMV infection. Type I IFN DNA coimmunisation may provide increased efficacy for viral vaccines and subsequently modulate post-viral chronic inflammatory disorders.
D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D007370:Interferon Type I / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus; D009205:Myocarditis / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014760:Viral Fusion Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage*
D007370:Interferon Type I; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; C040495:glycoprotein B, Simplexvirus