The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans.
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans.
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DOI：
10.1126/scitranslmed.abl8124
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发表时间：
2022-03-09
影响因子：
17.1
通讯作者：
Esser MT
中科院分区：
文献类型：
--
作者：
Loo YM;McTamney PM;Arends RH;Abram ME;Aksyuk AA;Diallo S;Flores DJ;Kelly EJ;Ren K;Roque R;Rosenthal K;Streicher K;Tuffy KM;Bond NJ;Cornwell O;Bouquet J;Cheng LI;Dunyak J;Huang Y;Rosenbaum AI;Pilla Reddy V;Andersen H;Carnahan RH;Crowe JE Jr;Kuehne AI;Herbert AS;Dye JM;Bright H;Kallewaard NL;Pangalos MN;Esser MT
尽管严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）疫苗取得了成功，但仍需要为仍处于2019冠状病毒病（COVID-19）风险中的个人提供更多预防和治疗选择。针对病毒刺突蛋白的单克隆抗体（mAb）有可能预防和治疗COVID-19，并降低严重疾病和死亡的风险。在这里，我们描述了AZD 7442，两种单克隆抗体的组合，AZD 8895（tixagevimab）和AZD 1061（cigavimab），同时结合刺突蛋白受体结合域上不同的，非重叠的表位，以中和SARS-CoV-2。这两种mAb最初是从先前感染SARS-CoV-2的个体中分离出来的，旨在延长其半衰期并降低效应功能。AZD 7442单克隆抗体可单独阻止刺突蛋白与血管紧张素转换酶2受体结合，阻断病毒进入细胞，并中和所有检测的SARS-CoV-2变异体。在SARS-CoV-2感染的非人灵长类动物模型中，预防性AZD 7442给药可预防感染，而治疗性给药可加速病毒从肺部清除。在一项正在进行的健康受试者I期研究（NCT 04507256）中，肌内注射300 mg AZD 7442可使SARS-CoV-2血清几何平均中和滴度高于恢复期血清10倍以上，持续至少3个月，在AZD 7442给药后9个月仍高于恢复期血清3倍。在鼻粘膜（SARS-CoV-2感染部位）中检测到约1%至2%的血清AZD 7442。对血清AZD 7442浓度的时间进程的外推表明，AZD 7442可提供长达12个月的保护，并使COVID-19高风险人群受益。AZD 7442可中和SARS-CoV-2，对NHP具有预防和治疗功效，预计将有助于长期保护人体。
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300 mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained 3-fold above those of convalescent serum at 9 months post-AZD7442 administration. Approximately 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19. AZD7442 neutralizes SARS-CoV-2, has prophylactic and therapeutic efficacy in NHPs, and is projected to contribute to long-term human protection.
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DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
影响因子：
4.9
作者：
Griffin MP;Khan AA;Esser MT;Jensen K;Takas T;Kankam MK;Villafana T;Dubovsky F
通讯作者：
Dubovsky F
REGN-COV2抗体预防和治疗恒河猕猴和仓鼠中的SARS-COV-2感染。
DOI：
10.1126/science.abe2402
发表时间：
2020-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baum A;Ajithdoss D;Copin R;Zhou A;Lanza K;Negron N;Ni M;Wei Y;Mohammadi K;Musser B;Atwal GS;Oyejide A;Goez-Gazi Y;Dutton J;Clemmons E;Staples HM;Bartley C;Klaffke B;Alfson K;Gazi M;Gonzalez O;Dick E Jr;Carrion R Jr;Pessaint L;Porto M;Cook A;Brown R;Ali V;Greenhouse J;Taylor T;Andersen H;Lewis MG;Stahl N;Murphy AJ;Yancopoulos GD;Kyratsous CA
通讯作者：
Kyratsous CA
DOI：
10.2215/cjn.03500321
发表时间：
2021-07-01
影响因子：
9.8
作者：
Grupper, Ayelet;Sharon, Nechama;Shashar, Moshe
通讯作者：
Shashar, Moshe
DOI：
10.1016/j.jaci.2021.05.029
发表时间：
2021-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Hagin D;Freund T;Navon M;Halperin T;Adir D;Marom R;Levi I;Benor S;Alcalay Y;Freund NT
通讯作者：
Freund NT