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

• Published in: Vaccine Vol. 26; no. 47; pp. 5922 - 5927
• Main Authors: Bakker, A.B.H., Python, C., Kissling, C.J., Pandya, P., Marissen, W.E., Brink, M.F., Lagerwerf, F., Worst, S., van Corven, E., Kostense, S., Hartmann, K., Weverling, G.J., Uytdehaag, F., Herzog, C., Briggs, D.J., Rupprecht, C.E., Grimaldi, R., Goudsmit, J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 05.11.2008; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Allergy and Immunology; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - immunology; Antibodies, Viral - administration & dosage; Antibodies, Viral - adverse effects; Antibodies, Viral - immunology; Applied microbiology; Biological and medical sciences; Body temperature; Cell Line; Double-Blind Method; Equine rabies immunoglobulin (ERIG); Female; Fundamental and applied biological sciences. Psychology; Human rabies immunoglobulin (HRIG); Humans; Immunization, Passive; Male; Microbiology; Middle Aged; Miscellaneous; Monoclonal antibodies; Neutralization Tests; Pain; Post-exposure prophylaxis; Prophylaxis; Rabies; Rabies - immunology; Rabies - prevention & control; Rabies Vaccines - administration & dosage; Rabies Vaccines - immunology; Rabies virus; Rabies virus - immunology; Studies; Treatment Outcome; Unmet medical need; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Virology; Young Adult; India; USA; Human rabies immunoglobulin (HRIG); Vaccination; Rabies; Equine rabies immunoglobulin (ERIG); Monoclonal antibodies; Post-exposure prophylaxis; Unmet medical need; Chemoprophylaxis; Monoclonal antibody; Rhabdoviridae; Horse; Ungulata; cywu,w. Vaccination; Human; Nervous system diseases; Immunoglobulins; Rabies virus; Infection; Virus; Mononegavirales; Vertebrata; Mammalia; Viral disease; Lyssavirus; Perissodactyla; Veterinary
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2008.08.050

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 1 to day 21 after a single dose 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.