Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.
Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.
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DOI：
10.1172/jci.insight.167464
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发表时间：
2023-07-24
期刊：
影响因子：
8
通讯作者：
Kent, Stephen J.
中科院分区：
文献类型：
--
作者：
Vanderven, Hillary A.;Wentworth, Deborah N.;Han, Win Min;Peck, Heidi;Barr, Ian G.;Davey, Jr Richard T.;Beigel, John H.;Dwyer, Dominic E.;Jain, Mamta K.;Angus, Brian;Brandt, Christian T.;Mykietiuk, Analia;Law, Matthew G.;Neaton, James D.;Kent, Stephen J.
以抗体为基础的呼吸道病毒疗法日益重要。Insight 006试验给因流感住院的患者注射了抗流感高免疫静脉免疫球蛋白(Flu-IVIG)。流感静脉注射免疫球蛋白治疗改善了乙型流感患者的预后，但对甲型流感无效。为了探讨流感静脉注射免疫球蛋白发挥作用的潜在机制，我们收集了甲型或乙型流感住院患者的血清，通过ELISA、基于微球的多重分析和NK细胞激活试验分析了抗体亚型/亚类和Fcγ受体(FcγR)结合情况。流感病毒特异性FcγR结合抗体在注射流感免疫球蛋白的传染性支气管炎和流行性出血热感染患者中升高。在感染传染性支气管炎病毒的参与者(n=62)中，IgG3和FcγR结合增加与更有利的结果相关。在抗IBV Fc功能抗体水平较低的患者中，Flu-IVIG治疗也提高了更有利的结果。在IAV感染患者中，较高的FcγR结合抗体与较差的预后相关(n=50)，而在抗IAVFc功能抗体水平较低的参与者中，Flu-IVIG降低了有利结果的几率。这些详细的血清学分析提供了对成功的流感体液反应所需的抗体特征和机制的洞察，表明具有Fc介导功能的IBV特异性抗体而不是IAV特异性抗体可能有助于改善流感结果。这项工作将为改进的流感免疫疗法的发展提供信息。临床试验.gov NCT02287467。这项研究的资金由分包合同13XS134提供，分包合同为Leidos生物医学研究主合同HHSN261200800001E和HHSN261201500003I，NCI/NIAID。
Antibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A. To probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays. Influenza-specific FcγR-binding antibodies were elevated in Flu-IVIG–infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody. These detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies. ClinicalTrials.gov NCT02287467. Funding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.
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DOI：
10.1073/pnas.1609316113
发表时间：
2016-10-18
影响因子：
11.1
作者：
He, Wenqian;Tan, Gene S.;Miller, Matthew S.
通讯作者：
Miller, Matthew S.
影响因子：
7.6
作者：
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通讯作者：
Sims, Amy C.
影响因子：
6.4
作者：
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通讯作者：
KARZON, DT
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影响因子：
30.3
作者：
Henry Dunand CJ;Leon PE;Huang M;Choi A;Chromikova V;Ho IY;Tan GS;Cruz J;Hirsh A;Zheng NY;Mullarkey CE;Ennis FA;Terajima M;Treanor JJ;Topham DJ;Subbarao K;Palese P;Krammer F;Wilson PC
通讯作者：
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影响因子：
5.4
作者：
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