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About the Authors:
Tzu-Yuan Chao
Roles Writing - original draft
* E-mail: [email protected]
Affiliation: Synermore Biologics Co., Ltd., Taipei, Taiwan
ORCID http://orcid.org/0000-0002-6781-7520
Shiqi Ren
Roles Data curation, Investigation
Affiliation: Synermore Biologics Co., Ltd., Taipei, Taiwan
Enyun Shen
Roles Methodology, Project administration
Affiliation: Beijing Cotimes Biotech Co., Ltd., Beijing, China
Susan Moore
Roles Investigation, Methodology
Affiliation: Kansas State University Rabies Laboratory, Manhattan, Kansas State, United States of America
Shou-feng Zhang
Roles Investigation, Methodology, Resources
Affiliation: Laboratory of Epidemiology and Key Laboratory of Jilin Provincial Zoonosis Control and Prevention, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, China
Li Chen
Roles Writing - review & editing
Affiliation: Synermore Biologics Co., Ltd., Taipei, Taiwan
Charles E. Rupprecht
Roles Methodology, Writing - review & editing
Affiliation: LYSSA LLC, Atlanta, Georgia, United States of America
Eric Tsao
Roles Funding acquisition, Supervision
Affiliation: Synermore Biologics Co., Ltd., Taipei, TaiwanAbstract
Rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (PEP). However, current PEP relies on polyclonal immune globulin products purified from pooled human (HRIG) or equine (ERIG) plasma that are either in chronic shortage or in association with safety concerns. Here, we present the development of an antibody cocktail, SYN023, made of two novel monoclonal antibodies (MAb) CTB011 and CTB012 that could serve as safer and more cost-effective alternatives to the current RIG products. Both CTB011 and CTB012 are humanized MAbs that bind to non-overlapping epitopes on the rabies virus (RABV) glycoprotein (G) with sub-nanomolar affinities. Sequence analysis revealed that many of the critical residues in binding are highly conserved across different species of lyssaviruses. When combined at a 1:1 ratio, CTB011/CTB012 exhibited neutralization capabilities equivalent or superior to HRIG against 10 North American street RABV isolates in vitro and 15 prevalent Chinese RABV strains in animal models. Finally, SYN023, at a dosage of 0.03 mg/kg, was able to offer the same degree of protection as standard HRIG administration (20 IU/kg) in Syrian hamsters challenged with a highly virulent bat (Tadarida brasiliensis) RABV variant. Taken together, the high-potency and broad-spectrum neutralization demonstrated by SYN023 make it an effective candidate for human rabies PEP consideration.
Author summary
Rabies is a preventable viral disease and yet human rabies is still prevalent in many less-developed parts of...