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....
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-03-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201505986 |
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| author | Paola De Benedictis Andrea Minola Elena Rota Nodari Roberta Aiello Barbara Zecchin Angela Salomoni Mathilde Foglierini Gloria Agatic Fabrizia Vanzetta Rachel Lavenir Anthony Lepelletier Emma Bentley Robin Weiss Giovanni Cattoli Ilaria Capua Federica Sallusto Edward Wright Antonio Lanzavecchia Hervé Bourhy Davide Corti |
| author_facet | Paola De Benedictis Andrea Minola Elena Rota Nodari Roberta Aiello Barbara Zecchin Angela Salomoni Mathilde Foglierini Gloria Agatic Fabrizia Vanzetta Rachel Lavenir Anthony Lepelletier Emma Bentley Robin Weiss Giovanni Cattoli Ilaria Capua Federica Sallusto Edward Wright Antonio Lanzavecchia Hervé Bourhy Davide Corti |
| author_sort | Paola De Benedictis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e80ee3d7220543d9872041b2b9068ffa |
| institution | DOAJ |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e80ee3d7220543d9872041b2b9068ffa2025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-03-018440742110.15252/emmm.201505986Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxisPaola De Benedictis0Andrea Minola1Elena Rota Nodari2Roberta Aiello3Barbara Zecchin4Angela Salomoni5Mathilde Foglierini6Gloria Agatic7Fabrizia Vanzetta8Rachel Lavenir9Anthony Lepelletier10Emma Bentley11Robin Weiss12Giovanni Cattoli13Ilaria Capua14Federica Sallusto15Edward Wright16Antonio Lanzavecchia17Hervé Bourhy18Davide Corti19FAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieHumabs BioMed SAFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieInstitute for Research in Biomedicine, Università della Svizzera ItalianaHumabs BioMed SAHumabs BioMed SAInstitut Pasteur, Unit of Lyssavirus Dynamics and Host Adaptation, National Reference Centre for Rabies, World Health Organization Collaborating Centre for Reference and Research on RabiesInstitut Pasteur, Unit of Lyssavirus Dynamics and Host Adaptation, National Reference Centre for Rabies, World Health Organization Collaborating Centre for Reference and Research on RabiesViral Pseudotype Unit, Faculty of Science and Technology, University of WestminsterDivision of Infection and Immunity, University College LondonFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieFAO and National Reference Centre for Rabies, National Reference Centre and OIE Collaborating Centre for Diseases at the Animal‐Human Interface, Istituto Zooprofilattico Sperimentale delle VenezieInstitute for Research in Biomedicine, Università della Svizzera ItalianaViral Pseudotype Unit, Faculty of Science and Technology, University of WestminsterInstitute for Research in Biomedicine, Università della Svizzera ItalianaInstitut Pasteur, Unit of Lyssavirus Dynamics and Host Adaptation, National Reference Centre for Rabies, World Health Organization Collaborating Centre for Reference and Research on RabiesHumabs BioMed SAAbstract 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.https://doi.org/10.15252/emmm.201505986human monoclonal antibodylyssavirusespost‐exposure prophylaxisrabies |
| spellingShingle | Paola De Benedictis Andrea Minola Elena Rota Nodari Roberta Aiello Barbara Zecchin Angela Salomoni Mathilde Foglierini Gloria Agatic Fabrizia Vanzetta Rachel Lavenir Anthony Lepelletier Emma Bentley Robin Weiss Giovanni Cattoli Ilaria Capua Federica Sallusto Edward Wright Antonio Lanzavecchia Hervé Bourhy Davide Corti Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis EMBO Molecular Medicine human monoclonal antibody lyssaviruses post‐exposure prophylaxis rabies |
| title | Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis |
| title_full | Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis |
| title_fullStr | Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis |
| title_full_unstemmed | Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis |
| title_short | Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis |
| title_sort | development of broad spectrum human monoclonal antibodies for rabies post exposure prophylaxis |
| topic | human monoclonal antibody lyssaviruses post‐exposure prophylaxis rabies |
| url | https://doi.org/10.15252/emmm.201505986 |
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