title: Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis.
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.
authors.affiliation: 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.
authors.forename: Paola
authors.initials: P
authors.lastname: De Benedictis
authors.affiliation: Humabs BioMed SA, Bellinzona, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Minola
authors.affiliation: 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.
authors.forename: Elena
authors.initials: E
authors.lastname: Rota Nodari
authors.affiliation: 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.
authors.forename: Roberta
authors.initials: R
authors.lastname: Aiello
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zecchin
authors.affiliation: 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.
authors.forename: Angela
authors.initials: A
authors.lastname: Salomoni
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Foglierini
authors.affiliation: Humabs BioMed SA, Bellinzona, Switzerland.
authors.forename: Gloria
authors.initials: G
authors.lastname: Agatic
authors.affiliation: Humabs BioMed SA, Bellinzona, Switzerland.
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Vanzetta
authors.affiliation: 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.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lavenir
authors.affiliation: 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.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lepelletier
authors.affiliation: Viral Pseudotype Unit, Faculty of Science and Technology, University of Westminster, London, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Bentley
authors.affiliation: Division of Infection and Immunity, University College London, London, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Weiss
authors.affiliation: 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.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cattoli
authors.affiliation: 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.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Capua
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Viral Pseudotype Unit, Faculty of Science and Technology, University of Westminster, London, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Wright
authors.affiliation: Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: 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.
authors.forename: Hervé
authors.initials: H
authors.lastname: Bourhy
authors.affiliation: Humabs BioMed SA, Bellinzona, Switzerland Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland davide.corti@humabs.ch.
authors.forename: Davide
authors.identifier: 0000-0003-4046-7222
authors.initials: D
authors.lastname: Corti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D008647:Mesocricetus; D056990:Post-Exposure Prophylaxis / Q000379:methods*; D011818:Rabies / Q000517:prevention & control*; D011820:Rabies virus / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007155:Immunologic Factors
keywords: human monoclonal antibody; lyssaviruses; post‐exposure prophylaxis; rabies