کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2403134 | 1102885 | 2012 | 11 صفحه PDF | دانلود رایگان |
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.
► Type I IFN is produced following single-cycle flavivirus (SCFV) vaccine immunization.
► Type I IFN severely restricts SCFV gene expression in wild type mice.
► Significant increase in CD8+ T cell response in the absence of type I IFN receptor.
► Altered patterns of cytokine production, but not virus-specific cytotoxicity, by WNV-specific CD8+ T cells in the absence of type I IFN receptor.
Journal: Vaccine - Volume 30, Issue 8, 14 February 2012, Pages 1465–1475