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 Milligan

Research output: Contribution to journalArticle

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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

Fingerprint

Interferon alpha-beta Receptor
Flavivirus
interferons
Vaccines
vaccines
West Nile virus
Interferon Type I
Interferons
receptors
T-Lymphocytes
mice
T-lymphocytes
Virus Diseases
live vaccines
Cytokines
Gene Expression
Antigens
Attenuated Vaccines
Wild Animals
Viral Antigens

Keywords

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

ASJC Scopus subject areas

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

Cite this

Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling. / Winkelmann, Evandro R.; Widman, Douglas G.; Xia, Jingya; Ishikawa, Tomohiro; Miller-Kittrell, Mindy; Nelson, Michelle H.; Bourne, Nigel; Scholle, Frank; Mason, Peter W.; Milligan, Gregg.

In: Vaccine, Vol. 30, No. 8, 14.02.2012, p. 1465-1475.

Research output: Contribution to journalArticle

Winkelmann, ER, Widman, DG, Xia, J, Ishikawa, T, Miller-Kittrell, M, Nelson, MH, Bourne, N, Scholle, F, Mason, PW & Milligan, G 2012, 'Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling', Vaccine, vol. 30, no. 8, pp. 1465-1475. https://doi.org/10.1016/j.vaccine.2011.12.103
Winkelmann ER, Widman DG, Xia J, Ishikawa T, Miller-Kittrell M, Nelson MH et al. Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling. Vaccine. 2012 Feb 14;30(8):1465-1475. https://doi.org/10.1016/j.vaccine.2011.12.103
Winkelmann, Evandro R. ; Widman, Douglas G. ; Xia, Jingya ; Ishikawa, Tomohiro ; Miller-Kittrell, Mindy ; Nelson, Michelle H. ; Bourne, Nigel ; Scholle, Frank ; Mason, Peter W. ; Milligan, Gregg. / Intrinsic adjuvanting of a novel single-cycle flavivirus vaccine in the absence of type I interferon receptor signaling. In: Vaccine. 2012 ; Vol. 30, No. 8. pp. 1465-1475.
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