Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
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DOI：
10.1016/j.cell.2016.09.049
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发表时间：
2016-10-20
期刊：
影响因子：
64.5
通讯作者：
Crowe, James E., Jr.
中科院分区：
文献类型：
--
作者：
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., Jr.
猴痘(MPXV)和牛痘(CPXV)是间歇性引起严重人类感染的新兴病原体，而天花病毒(VARV)有可能被用作生物恐怖的病原体。痘苗免疫球蛋白(VIG)已被用于治疗严重的正痘病毒感染，但供应不足。我们从免疫受试者中产生了一大批正痘病毒特异性的人类单抗(Abs)，以研究对各种正痘病毒的广泛中和抗体反应的分子基础。详细的分析揭示了与VACV、CPXV、MPXV和VARV交叉反应的主要中和抗体特异性，这些抗体是小鼠攻击模型中保护的决定因素。呼吸道或全身感染后的最佳保护需要以几种膜蛋白为靶点的抗体的混合物，包括包膜和成熟病毒粒子形式的病毒上的蛋白。这项工作揭示了人类抗体的正痘病毒靶点，介导了交叉保护免疫，并确定了新的候选抗体治疗混合物以取代VIG。针对天花和正痘病毒家族其他成员的保护性免疫需要抗体的合作，这些抗体在病毒成熟的不同阶段针对不同的病毒蛋白。
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. Protective immunity against smallpox and other members of the orthopoxvirus family requires the cooperation of antibodies that target different viral proteins at distinct stages of maturation of the virus.
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影响因子：
1.2
作者：
McCausland MM;Benhnia MR;Crickard L;Laudenslager J;Granger SW;Tahara T;Kubo R;Koriazova L;Kato S;Crotty S
通讯作者：
Crotty S
影响因子：
5.4
作者：
Benhnia, Mohammed Rafii-El-Idrissi;McCausland, Megan M.;Crotty, Shane
通讯作者：
Crotty, Shane
影响因子：
6.4
作者：
Kennedy, Jeffrey S.;Gurwith, Marc;Greenberg, Richard N.
通讯作者：
Greenberg, Richard N.
DOI：
10.1073/pnas.0408782102
发表时间：
2005-01-18
影响因子：
11.1
作者：
Davies, DH;Liang, XW;Felgner, PL
通讯作者：
Felgner, PL
DOI：
10.1073/pnas.1233578100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Belyakov, IM;Earl, P;Berzofsky, JA
通讯作者：
Berzofsky, JA