Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle East Respiratory Syndrome Coronavirus.
Human Monoclonal Antibody Cocktail for the Treatment or Prophylaxis of Middle East Respiratory Syndrome Coronavirus.
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DOI：
10.1093/infdis/jiab036
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发表时间：
2022-05-16
期刊：
影响因子：
--
通讯作者：
Lipsich L
中科院分区：
文献类型：
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作者：
Sivapalasingam S;Saviolakis GA;Kulcsar K;Nakamura A;Conrad T;Hassanein M;Sumner G;Elango C;Kamal MA;Eng S;Kyratsous CA;Musser BJ;Frieman M;Kantrowitz J;Weinreich DM;Yancopoulos G;Stahl N;Lipsich L
REGN 3048和REGN 3051是靶向中东呼吸综合征冠状病毒（MERS-CoV）上刺突糖蛋白的人单克隆抗体（mAb），其与受体二肽基肽酶-4（DPP 4）结合，是感染易感细胞所必需的。临床前研究：在MERS-CoV（Jordan株）感染前1天和感染后1天，向人源化DPP 4（huDPP 4）小鼠给予REGN 3048、REGN 3051和同种型免疫球蛋白G（IgG）。评估病毒滴度和肺病理学。1期研究：健康成人接受联合mAb（n = 36）或安慰剂（n = 12），并随访121天。 研究了6个剂量水平。剂量递增前符合严格的安全标准。临床前研究：与对照抗体和每种抗体单药治疗相比，REGN 3048加REGN 3051在治疗或治疗上显著更有效地降低huDPP 4小鼠的病毒滴度、肺部炎症和病理学。I期研究：REGN 3048 + REGN 3051耐受性良好，无剂量限制性不良事件、死亡、严重不良事件或输注反应。每种mAb均显示人IgG 1抗体的预期药代动力学;其无免疫原性。REGN 3048和REGN 3051联合给药耐受性良好。临床和临床前数据支持进一步开发MERS-CoV感染的治疗或预防。REGN 3048和REGN 3051联合给药耐受性良好。每种单克隆抗体均显示人IgG 1抗体的预期药代动力学;其无免疫原性。临床和临床前数据支持进一步开发REGN 3048和REGN 3051用于治疗或预防MERS-CoV感染。
REGN3048 and REGN3051 are human monoclonal antibodies (mAb) targeting the spike glycoprotein on the Middle East respiratory syndrome coronavirus (MERS-CoV), which binds to the receptor dipeptidyl peptidase-4 (DPP4) and is necessary for infection of susceptible cells. Preclinical study: REGN3048, REGN3051 and isotype immunoglobulin G (IgG) were administered to humanized DPP4 (huDPP4) mice 1 day prior to and 1 day after infection with MERS-CoV (Jordan strain). Virus titers and lung pathology were assessed. Phase 1 study: healthy adults received the combined mAb (n = 36) or placebo (n = 12) and followed for 121 days. Six dose levels were studied. Strict safety criteria were met prior to dose escalation. Preclinical study: REGN3048 plus REGN3051, prophylactically or therapeutically, was substantially more effective for reducing viral titer, lung inflammation, and pathology in huDPP4 mice compared with control antibodies and to each antibody monotherapy. Phase 1 study: REGN3048 plus REGN3051 was well tolerated with no dose-limiting adverse events, deaths, serious adverse events, or infusion reactions. Each mAb displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic. REGN3048 and REGN3051 in combination were well tolerated. The clinical and preclinical data support further development for the treatment or prophylaxis of MERS-CoV infection. REGN3048 and REGN3051 in combination were well tolerated. Each monoclonal antibody displayed pharmacokinetics expected of human IgG1 antibodies; it was not immunogenic. Clinical and preclinical data support further development of REGN3048 and REGN3051 for the treatment or prophylaxis of MERS-CoV infection.
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DOI：
10.1073/pnas.1324022111
发表时间：
2014-04-08
影响因子：
11.1
作者：
Murphy, Andrew J.;Macdonald, Lynn E.;Yancopoulos, George D.
通讯作者：
Yancopoulos, George D.
影响因子：
8
作者：
Null, D;Bimle, C;Top, FH
通讯作者：
Top, FH
影响因子：
5.3
作者：
Betts, Alison;Keunecke, Anne;Berkhout, Jan
通讯作者：
Berkhout, Jan
影响因子：
7.6
作者：
de Wit E;Feldmann F;Okumura A;Horne E;Haddock E;Saturday G;Scott D;Erlandson KJ;Stahl N;Lipsich L;Kyratsous CA;Feldmann H
通讯作者：
Feldmann H
DOI：
10.1056/nejmoa1910993
发表时间：
2019-12-12
期刊：
The New England journal of medicine
影响因子：
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作者：
通讯作者：
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