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

Gene Therapy volume 9, pages 1369–1378 (2002)Cite this article

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 × 104 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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Acknowledgements

We are especially grateful to VICAL for providing the pkCMVint mammalian expression vector. This work was supported by the National Health and Medical Research Council of Australia (project grant No. 990393).

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  1. Division of Veterinary and Biomedical Sciences, Western Australian Biomedical Research Institute, Murdoch University, Perth, Western Australia

    V S Cull, S Broomfield, E J Bartlett, N L Brekalo & C M James

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Cull, V., Broomfield, S., Bartlett, E. et al. Coimmunisation with type I IFN genes enhances protective immunity against cytomegalovirus and myocarditis in gB DNA-vaccinated mice. Gene Ther 9, 1369–1378 (2002). https://doi.org/10.1038/sj.gt.3301809

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