Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.
Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.
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结合Gp120和Gp41的双特异性抗HIV免疫粘附素具有广泛和有效的HIV中和活性。
DOI：
10.3390/vaccines9070774
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发表时间：
2021-07-12
期刊：
影响因子：
7.8
通讯作者：
Kozlowski PA
中科院分区：
文献类型：
--
作者：
Pincus SH;Craig RB;Weachter L;LaBranche CC;Nabi R;Watt C;Raymond M;Peters T;Song K;Maresh GA;Montefiori DC;Kozlowski PA
我们已经构建了双特异性免疫球蛋白样免疫粘附素，其结合HIV包膜糖蛋白：gp 120和gp 41。这些免疫粘附素具有移植到人抗gp 41 mAb 7 B2重链N末端的人CD 4 N末端结构域。将这些构建体与重组Env的结合及其抗病毒活性与亲本mAb和CD 4以及对照mAb的结合及其抗病毒活性进行比较。CD 4/7 B2构建体结合gp 41和gp 140，以及感染细胞表面表达的天然Env。这些构建体将细胞毒性免疫缀合物递送至HIV感染的细胞，但不如7 B2和sCD 4的混合物，并调理抗体介导的吞噬作用。最令人惊讶的是，考虑到7 B2弱中和（如果有的话），嵌合的CD 4/7 B2免疫粘附素表现出与公知的中和mAb相当的广泛和有效的HIV中和。这些数据增加了越来越多的证据表明，增强的中和活性可以获得双功能单克隆抗体/免疫粘附素。CD 4/7 B2嵌合体的增强的中和活性可能是由于两个Env亚基的交联以及随后对进入所必需的融合前构象事件的抑制。
We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to recombinant Env and their antiviral activities were compared to that of the parental mAbs and CD4, as well as to control mAbs. The CD4/7B2 constructs bind to both gp41 and gp140, as well as to native Env expressed on the surface of infected cells. These constructs deliver cytotoxic immunoconjugates to HIV-infected cells, but not as well as a mixture of 7B2 and sCD4, and opsonize for antibody-mediated phagocytosis. Most surprisingly, given that 7B2 neutralizes weakly, if at all, is that the chimeric CD4/7B2 immunoadhesins exhibit broad and potent neutralization of HIV, comparable to that of well-known neutralizing mAbs. These data add to the growing evidence that enhanced neutralizing activity can be obtained with bifunctional mAbs/immunoadhesins. The enhanced neutralization activity of the CD4/7B2 chimeras may result from cross-linking of the two Env subunits with subsequent inhibition of the pre-fusion conformational events that are necessary for entry.
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影响因子：
64.5
作者：
Bournazos S;Gazumyan A;Seaman MS;Nussenzweig MC;Ravetch JV
通讯作者：
Ravetch JV
影响因子：
5.9
作者：
Grobben, Marloes;Al Stuart, Richard;van Gils, Marit J.
通讯作者：
van Gils, Marit J.
影响因子：
5.4
作者：
Dey, B;Del Castillo, CS;Berger, EA
通讯作者：
Berger, EA
影响因子：
4.8
作者：
Hinton, PR;Johlfs, MG;Tsurushita, N
通讯作者：
Tsurushita, N
影响因子：
5.4
作者：
Chen, Weizao;Feng, Yang;Dimitrov, Dimiter S.
通讯作者：
Dimitrov, Dimiter S.