First administration to humans of a monoclonal antibody cocktail against rabies virus: Safety, tolerability, and neutralizing activity

被引：103

作者：

Bakker, A. B. H. ^{[1
]}

Python, C. ^{[2
]}

Kissling, C. J. ^{[3
]}

Pandya, P. ^{[4
]}

Marissen, W. E. ^{[1
]}

Brink, M. F. ^{[1
]}

Lagerwerf, F. ^{[1
]}

Worst, S. ^{[1
]}

van Corven, E. ^{[1
]}

Kostense, S. ^{[1
]}

Hartmann, K. ^{[2
]}

Weverling, G. J. ^{[1
]}

Uytdehaag, F. ^{[1
]}

Herzog, C. ^{[2
]}

Briggs, D. J. ^{[5
]}

Rupprecht, C. E. ^{[6
]}

Grimaldi, R. ^{[1
]}

Goudsmit, J. ^{[1
]}

机构：

[1] Crucell Holland BV, NL-2301 CA Leiden, Netherlands

[2] Berna Biotech Ltd, Crucell, Bern, Switzerland

[3] MDS Pharma Serv, Lincoln, NE USA

[4] Dhirubhai Ambani Life Sci Ctr, Reliance Clin Pharmacol & Pharmacokinet Facil, RelClin, Navi Mumbai, India

[5] Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA

[6] Ctr Dis Control & Prevent, Rabies Sect, Div Viral & Rickettsial Dis, Atlanta, GA USA

来源：

VACCINE | 2008年 / 26卷 / 47期

关键词：

Vaccination; Rabies; Post-exposure prophylaxis; Monoclonal antibodies; Unmet medical need; Human rabies immunoglobulin (HRIG); Equine rabies immunoglobulin (ERIG);

D O I：

10.1016/j.vaccine.2008.08.050

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：5922 / 5927

页数：6

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