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Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis
Open accessAbstract
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.
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“Fourthly, the effective dose of an antibody is strongly dependent on its characteristics, that is, potential limitations may be overcome with the right protein (De Benedictis et al, 2016).”
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Metadata
- Authors
- De Benedictis, P., Minola, A., Rota Nodari, E., Aiello, R., Zecchin, B., Salomoni, A., Foglierini, M., Agatic, G., Vanzetta, F., Lavenir, R., Lepelletier, A., Bentley, E., Weiss, R., Cattoli, G., Capua, I., Sallusto, F., Wright, E., Lanzavecchia, A., Bourhy, H., & Corti, D.
- Affiliations
- Food and Agriculture Organization of the United Nations (IT)
- Institute for Research in Biomedicine (CH)
- Institut Pasteur (FR)
- University of Westminster (GB)
- University College London (GB)
- ETH Zurich (CH)
- Corresponding author
- Corti, Davide
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2016-03-18
- Volume
- 8
- Issue
- 4
- Pages
- 407-421
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC4818751
- OpenAlex
- W2298668359
- Cited by
- 103
- References
- 63
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 5 · 2020: 14 · 2019: 2 · 2018: 16 · 2017: 9 · 2016: 3
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- WestminsterResearch (University of Westminster) (acceptedVersion)
- WestminsterResearch (University of Westminster) (acceptedVersion, cc-by)
- reroDoc Digital Library (submittedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Italian Ministry of Health (RC IZSVe 08/2009)
- Helmut Horten Foundation
- Swiss Vaccine Research Institute
- FAO/National RC for Rabies, IZSVe‐Italy
- IAEA Laboratories‐Austria
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- rabies post-exposure prophylaxis, human monoclonal antibodies, broadly neutralizing antibodies, rabies virus, lyssaviruses, memory B cells, antibody epitope specificity, neutralizing activity
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibodies, Viral, Disease Models, Animal, Humans, Immunization, Passive, Immunologic Factors, Mesocricetus, Rabies, Rabies virus, Survival Analysis, Treatment Outcome, Post-Exposure Prophylaxis, Antibodies, Neutralizing
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