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

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• 作者：Evandro R. Winkelmann^a ; ¹ ; Douglas G. Widman^b ; ¹ ; ² ; Jingya Xia^b ; Tomohiro Ishikawa^a ; ³ ; Mindy Miller-Kittrell^c ; Michelle H. Nelson^b ; Nigel Bourne^b ; ^d ; ^e ; Frank Scholle^c ; Peter W. Mason^a ; ^b ; ^d ; ⁴ ; Gregg N. Milligan^b ; ^d ; ^e ; ^{gnmillig@utmb.edu}
• 关键词：ASC ; antibody secreting cell ; B6 ; C57BL/6 mice ; FLUC ; firefly luciferase ; FP ; footpad ; hpi ; hours post-immunization ; IFNAR&minus ; /&minus ; IFN-¦Á ; ¦Â receptor knockout mouse ; ISG ; IFN-stimulated gene ; LN ; lymph node ; PRR ; pattern recognition receptor ; SCFV
• 刊名：Vaccine
• 出版年：2012
• 出版时间：14 February 2012
• 年：2012
• 卷：30
• 期：8
• 页码：1465-1475
• 全文大小：1341 K

文摘

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-¦Á 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^{??/sup>) compared to wild-type (wt) mice indicating a profound IFN-mediated suppression of SCFV gene expression in the wt animals. IFNAR??/sup> 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??/sup> mice and a significantly greater percentage of these T cells from IFNAR??/sup> mice produced only IFN-¦Ã 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.}