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Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice.

Authors
  • Cull, V S
  • Broomfield, S
  • Bartlett, E J
  • Brekalo, N L
  • James, C M
Type
Published Article
Journal
Gene Therapy
Publisher
Springer Nature
Publication Date
Oct 01, 2002
Volume
9
Issue
20
Pages
1369–1378
Identifiers
PMID: 12365002
Source
Medline
License
Unknown

Abstract

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.

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