Cited by 103Rabies epidemiology and controlMonoclonal and Polyclonal Antibodies ResearchVirology and Viral Diseases

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

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De Benedictis, Paola, Minola, Andrea, Rota Nodari, Elena, Aiello, Roberta, Zecchin, Barbara, Salomoni, Angela, Foglierini, Mathilde, Agatic, Gloria +12 more·2016·EMBO Molecular Medicine

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.

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Crossref · 10.15252/emmm.201505986

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  • The effective dose of an antibody is strongly dependent on its characteristics, so potential limitations may be overcome with the right protein (De Benedictis et al, 2016).

    “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).”

    From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as De Benedictis et al, 2016

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Research works printed but not linked: 4

  1. Atanasiu P, Cannon DA, Dean DJ, Fox JP, Habel K, Kaplan MM, Kissling RE, Koprowski H, Lepine P, Perez Gallardo F (1961) Rabies neutralizing antibody response to different schedules of serum and vaccine inoculations in non‐exposed persons. 3. Bull World Health Organ 25: 103– 114 13863061 PMC2555550
  2. Atanasiu P, Dean DJ, Habel K, Kaplan MM, Koprowski H, Lepine P, Serie C (1967) Rabies neutralizing antibody response to different schedules of serum and vaccine inoculations in non‐exposed persons. 4. Bull World Health Organ 36: 361– 365 5299668 PMC2476304
  3. Dietzgen R, Calisher C, Kurath G, Kuzmin I, Rodriguez L, Stone D, Tesh R, Tordo N, Walker P, Wetzel T et al (2011) Rhabdoviridae In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ (eds), pp 686– 714. Oxford, UK: Elsevier
  4. Kitasato BU (1890) Ueber das Zustandekommender Diphterie‐Immunitat und der Tetanus‐Immunitat. Deutsche Medizinische Wochenschrift 5843503

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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
Venue
EMBO Molecular Medicine
Published
2016-03-18
Volume
8
Issue
4
Pages
407-421
ISSN
  • 1757-4676 (ISSN-L)
  • 1757-4684
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
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
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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