Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling

Evandro R. Winkelmann, Douglas G. Widman, Jingya Xia, Tomohiro Ishikawa, Mindy Miller-Kittrell, Michelle H. Nelson, Nigel Bourne, Frank Scholle, Peter W. Mason, Gregg N. Milligan

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Type I interferons (IFNs) are critical for controlling pathogenic virus infections and can enhance immune responses. Hence their impact on the effectiveness of live-attenuated vaccines involves a balance between limiting viral antigen expression and enhancing the development of adaptive immune responses. We examined the influence of type I IFNs on these parameters following immunization with RepliVAX WN, a single-cycle flavivirus vaccine (SCFV) against West Nile virus (WNV) disease. RepliVAX WN-immunized mice produced IFN-α and displayed increased IFN-stimulated gene transcription in draining lymph nodes (LN). SCFV gene expression was over 100 fold-higher on days 1-3 post-infection in type I IFN receptor knockout mice (IFNAR -/-) compared to wild-type (wt) mice indicating a profound IFN-mediated suppression of SCFV gene expression in the wt animals. IFNAR -/- mice produced nearly equivalent levels of WNV-specific serum IgG and WNV-specific CD4 + T cell responses compared to wt mice. However, significantly higher numbers of WNV-specific CD8 + T cells were produced by IFNAR -/- mice and a significantly greater percentage of these T cells from IFNAR -/- mice produced only IFN-γ following antigen-specific re-stimulation. This altered cytokine expression was not associated with increased antigen load suggesting the loss of type I IFN receptor signaling was responsible for the altered quality of the CD8 + effector T cell response. Together, these results indicate that although type I IFN is not essential for the intrinsic adjuvanting of RepliVAX WN, it plays a role in shaping the cytokine secretion profiles of CD8 + effector T cells elicited by this SCFV.

Original languageEnglish (US)
Pages (from-to)1465-1475
Number of pages11
JournalVaccine
Volume30
Issue number8
DOIs
StatePublished - Feb 14 2012

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Keywords

  • CD8 T cell
  • Single-cycle virus
  • Type I IFN
  • West Nile virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Winkelmann, E. R., Widman, D. G., Xia, J., Ishikawa, T., Miller-Kittrell, M., Nelson, M. H., Bourne, N., Scholle, F., Mason, P. W., & Milligan, G. N. (2012). Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling. Vaccine, 30(8), 1465-1475. https://doi.org/10.1016/j.vaccine.2011.12.103