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EMBO Mol Med. 2016 Apr 1;8(4):407-21. doi: 10.15252/emmm.201505986.

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.

Author information

1
FAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal-Human Interface, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Padua, Italy.
2
Humabs BioMed SA, Bellinzona, Switzerland.
3
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
4
Institut Pasteur, Unit of Lyssavirus Dynamics and Host Adaptation National Reference Centre for Rabies World Health Organization Collaborating Centre for Reference and Research on Rabies, Paris Cedex 15, France.
5
Viral Pseudotype Unit, Faculty of Science and Technology, University of Westminster, London, UK.
6
Division of Infection and Immunity, University College London, London, UK.
7
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
8
Humabs BioMed SA, Bellinzona, Switzerland Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland davide.corti@humabs.ch.

Abstract

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.

KEYWORDS:

human monoclonal antibody; lyssaviruses; post‐exposure prophylaxis; rabies

PMID:
26992832
PMCID:
PMC4818751
DOI:
10.15252/emmm.201505986
[Indexed for MEDLINE]
Free PMC Article

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