Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV.
Systems Vaccinology Identifies an Early Innate Immune Signature as a Correlate of Antibody Responses to the Ebola Vaccine rVSV-ZEBOV.
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DOI：
10.1016/j.celrep.2017.08.023
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发表时间：
2017-08-29
期刊：
影响因子：
8.8
通讯作者：
Addo MM
中科院分区：
文献类型：
--
作者：
Rechtien A;Richert L;Lorenzo H;Martrus G;Hejblum B;Dahlke C;Kasonta R;Zinser M;Stubbe H;Matschl U;Lohse A;Krähling V;Eickmann M;Becker S;VEBCON Consortium;Thiébaut R;Altfeld M;Addo MM
预测疫苗功效仍然是一个挑战。我们使用系统疫苗学方法来识别接受埃博拉疫苗 rVSV-ZEBOV 的人类中抗体诱导的早期先天免疫相关性。分析第 0、1、3、7 和 14 天的血液样本中细胞因子水平、先天免疫细胞亚群和基因表达的变化。综合统计分析与交叉验证确定了 5 个早期先天标记的特征，这些标记与第 28 天及以后的抗体滴度相关。其中，第3天的IP-10和第1天NK细胞上CXCR6的MFI是独立相关的。我们一致发现了与 IP-10 相关的早期基因表达特征。对人类 rVSV-ZEBOV 疫苗早期先天免疫反应的全面表征揭示了与 IP-10 相关的免疫特征。这些结果表明了疫苗诱导抗体诱导的相关性，并为探索通过操纵 IP-10 增强疫苗有效性的策略提供了理论基础。 5 个早期先天标记与疫苗接种后第 3 天对埃博拉疫苗 rVSV-ZEBOV IP-10 的抗体反应相关，是抗体诱导的独立相关性 RNA-seq 分析识别了与 IP-10 Rechtien 等人相关的早期基因表达特征。应用系统疫苗学方法来检查埃博拉疫苗 rVSV-ZEBOV 引发的早期先天免疫反应。他们发现，以 IP-10 作为独立可溶性标记的早期先天免疫反应与 EBOV-GP 特异性抗体诱导相关。
Predicting vaccine efficacy remains a challenge. We used a systems vaccinology approach to identify early innate immune correlates of antibody induction in humans receiving the Ebola vaccine rVSV-ZEBOV. Blood samples from days 0, 1, 3, 7, and 14 were analyzed for changes in cytokine levels, innate immune cell subsets, and gene expression. Integrative statistical analyses with cross-validation identified a signature of 5 early innate markers correlating with antibody titers on day 28 and beyond. Among those, IP-10 on day 3 and MFI of CXCR6 on NK cells on day 1 were independent correlates. Consistently, we found an early gene expression signature linked to IP-10. This comprehensive characterization of early innate immune responses to the rVSV-ZEBOV vaccine in humans revealed immune signatures linked to IP-10. These results suggest correlates of vaccine-induced antibody induction and provide a rationale to explore strategies for augmenting the effectiveness of vaccines through manipulation of IP-10. 5 early innate markers correlate with antibody response to Ebola vaccine rVSV-ZEBOV IP-10 on day 3 after vaccination is an independent correlate of antibody induction RNA-seq analysis identifies early gene expression signature linked to IP-10 Rechtien et al. apply a systems vaccinology approach to examine the early innate immune responses elicited by the Ebola vaccine rVSV-ZEBOV. They find that early innate immune responses, with IP-10 as an independent soluble marker, correlate with EBOV-GP-specific antibody induction.
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