First administration to humans of a monoclonal antibody cocktail against rabies virus: Safety, tolerability, and neutralizing activity
First administration to humans of a monoclonal antibody cocktail against rabies virus: Safety, tolerability, and neutralizing activity
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DOI：
10.1016/j.vaccine.2008.08.050
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发表时间：
2008-11-05
期刊：
影响因子：
5.5
通讯作者：
Goudsmit, J.
中科院分区：
文献类型：
--
作者：
Bakker, A. B. H.;Python, C.;Goudsmit, J.
由于人或马狂犬病免疫球蛋白（分别为HRIG和ERIG）的供应有限，作为狂犬病暴露后预防（PEP）的一部分，通常无法提供即时被动免疫预防。我们报告了两项I期研究的首个临床数据，评估了一种单克隆鸡尾酒抗体CL184抗狂犬病。研究对象包括美国和印度的健康成人，分为两部分。首先，在一项双盲、随机、剂量递增的试验中，受试者接受单次肌肉注射CL184或安慰剂。第二，开放标签CL184 （20 IU/kg）与狂犬病疫苗联合施用。安全性是主要目标，以狂犬病病毒中和活性（RVNA）作为疗效指标。不到40%的受试者报告CL184注射部位疼痛；未见发热或局部硬化、红肿。CL184单次关闭20或40 IU/kg后，第1天至第21天均可检测到RVNA。从第14天起，所有受试者在联合接种狂犬病疫苗后，RVNA水平均达到足够水平（bb0 ~ 0.5 IU/mL）。CL184作为PEP中RIG的替代品似乎很有希望。(C) 2008 Elsevier Ltd版权所有。
Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies.The Studies included healthy adult subjects in the USA and India and involved two parts. First, subjects received a single intramuscular dose of CL184 or placebo in a double blind, randomized, dose-escalation trial. Second, open-label CL184 (20 IU/kg)was co-administered with rabies vaccine. Safety was the primary objective and rabies Virus neutralizing activity (RVNA) was investigated as efficacy parameter.Pain at the CL184 injection site was reported by less than 40% of subjects; no fever or local induration, redness or swelling was observed. RVNA was detectable from day I to day 21 after a single close of CL184 20 or 40 IU/kg. All subjects had adequate (>0.5 IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP. (C) 2008 Elsevier Ltd. All rights reserved.