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针对痘病毒感染的交叉中和及保护性人类抗体特异性

Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.

作者信息

Gilchuk Iuliia, Gilchuk Pavlo, Sapparapu Gopal, Lampley Rebecca, Singh Vidisha, Kose Nurgun, Blum David L, Hughes Laura J, Satheshkumar Panayampalli S, Townsend Michael B, Kondas Ashley V, Reed Zachary, Weiner Zachary, Olson Victoria A, Hammarlund Erika, Raue Hans-Peter, Slifka Mark K, Slaughter James C, Graham Barney S, Edwards Kathryn M, Eisenberg Roselyn J, Cohen Gary H, Joyce Sebastian, Crowe James E

机构信息

The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Veterans Administration Tennessee Valley Healthcare System, Nashville, TN 37332, USA.

出版信息

Cell. 2016 Oct 20;167(3):684-694.e9. doi: 10.1016/j.cell.2016.09.049.

DOI:10.1016/j.cell.2016.09.049
PMID:27768891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5093772/
Abstract

Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

摘要

猴痘病毒(MPXV)和牛痘病毒(CPXV)是间歇性导致人类严重感染的新出现病原体,而天花病毒(VARV)有被用作生物恐怖制剂的可能。牛痘免疫球蛋白(VIG)已被用于治疗严重的正痘病毒感染,但供应短缺。我们从免疫个体中产生了大量正痘病毒特异性人单克隆抗体(Abs),以研究针对多种正痘病毒的广泛中和抗体反应的分子基础。详细分析揭示了对痘苗病毒(VACV)、牛痘病毒、猴痘病毒和天花病毒具有交叉反应性的主要中和抗体特异性,这些特异性是小鼠攻毒模型中保护作用的决定因素。呼吸道或全身感染后的最佳保护需要靶向多种膜蛋白的抗体混合物,这些膜蛋白包括病毒包膜形式和成熟病毒体形式上的蛋白。这项工作揭示了介导交叉保护性免疫的人抗体的正痘病毒靶点,并确定了替代VIG的新候选抗体治疗混合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/ab0604197adf/gr7_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/bde7197cfd38/gr3_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/f77acadac5a5/gr4_lrg.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/52bbd3c3dc66/figs5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/41a856a6ecfd/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/ab0604197adf/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/e7f518581a3a/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/4348f889f8cb/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/4eef0b1c645a/figs1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/cc7088fb6358/figs2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/9713f2ad24e7/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/bde7197cfd38/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/f4e3362f72c5/figs3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/f77acadac5a5/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/61e40b5aa5b6/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/1653c05ec243/figs4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/52bbd3c3dc66/figs5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/41a856a6ecfd/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34aa/9534047/ab0604197adf/gr7_lrg.jpg

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