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Monoclonal antibodies for the prevention of rabies: theory and clinical practice

Authors Nagarajan T, Marissen W, Rupprecht C

Received 20 August 2013

Accepted for publication 1 October 2013

Published 20 January 2014 Volume 2014:4 Pages 1—12


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Thirumeni Nagarajan,1 Wilfred E Marissen,2 Charles E Rupprecht3,4

1Biological E. Limited, Shameerpet, Hyderabad, Andhra Pradesh, India; 2Crucell Holland BV, Leiden, the Netherlands; 3Ross University School of Veterinary Medicine, Biomedical Sciences, Basseterre, St. Kitts, West Indies; 4The Global Alliance For Rabies Control, Manhattan, KS, USA

Abstract: Monoclonal antibodies (MAbs) have become a unique and attractive class of biologics, possessing several desirable characteristics for use in human medicine. Anti-infective MAbs for several medically important viral agents, including rabies virus (RABV), have been developed and are currently at different stages of clinical development. Rabies is a vaccine-preventable but neglected zoonosis. After severe bite exposures, prompt administration of a combination of potent rabies vaccine and rabies immunoglobulin (RIG) is recommended. Due in part to cost, equine RIG has been largely used instead of human RIG, especially in the developing world. With an estimated 10 million RABV exposures annually, the use of MAbs has emerged in concept as a potential alternative to polyclonal RIG for future prophylaxis needs. Murine MAbs, although efficacious, are less attractive because of immunogenicity. However, human MAbs seem to have the potential to replace polyclonal RIG because they possess all the desirable characteristics for an intended biologic. The exquisite specificity of the MAbs for a single epitope is generally believed to result in narrow spectrum of RABV neutralization and perceived generation of escape mutants. These issues can be mitigated by formulating a cocktail of candidate MAbs that are directed against distinct, nonoverlapping epitopes. Expression of recombinant human MAbs in mammalian cell lines, such as Chinese hamster ovary and human retinal, is central to the economical production at an industrial scale. Thus far, human MAbs developed by two companies have successfully passed through Phase I or II clinical trials in countries such as the US and India.

Keywords: rabies, postexposure prophylaxis, polyclonal RIG, monoclonal antibody, rabies immunoglobulin, clinical trials

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