Development of novel canine phage display-derived neutralizing monoclonal antibody fragments against rabies virus from immunized dogs
File(s)
Published version
Author(s)
Chorpunkul, Apidsada
Boonyuen, Usa
Limkittikul, Kriengsak
Saengseesom, Wachiraporn
Phongphaew, Wallaya
Type
Journal Article
Abstract
Animal rabies is a potentially fatal infectious disease in mammals, especially dogs. Currently, the number of rabies cases in pet dogs is increasing in several regions of Thailand. However, no passive postexposure prophylaxis (PEP) has been developed to combat rabies infection in animals. As monoclonal antibodies (MAbs) are promising biological therapies for postinfection, we developed a canine-neutralizing MAb against rabies virus (RABV) via the single-chain variable fragment (scFv) platform. Immunized phage-displaying scFv libraries were constructed from PBMCs via the pComb3XSS system. Diverse canine VHVLκ and VHVLλ libraries containing 2.4 × 108 and 1.3 × 106 clones, respectively, were constructed. Five unique clones that show binding affinity with the RABV glycoprotein were then selected, of which K9RABVscFv1 and K9RABVscFv16 showed rapid fluorescent foci inhibition test (RFFIT) neutralizing titers above the human protective level of 0.5 IU/ml. Finally, in silico docking predictions revealed that the residues on the CDRs of these neutralizing clones interact mainly with similar antigenic sites II and III on the RABV glycoprotein. These candidates may be used to develop complete anti-RABV MAbs as a novel PEP protocol in pet dogs and other animals.
Date Issued
2024-10-03
Date Acceptance
2024-09-16
Citation
Scientific Reports, 2024, 14
ISSN
2045-2322
Publisher
Nature Portfolio
Journal / Book Title
Scientific Reports
Volume
14
Copyright Statement
© The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39358469
PII: 10.1038/s41598-024-73339-2
Subjects
ANTIGENIC SITE-III
CONSTRUCTION
GENERATION
GLYCOPROTEIN
IMMUNOGLOBULIN
LIBRARY
Multidisciplinary Sciences
REPERTOIRE
SCFV
Science & Technology
Science & Technology - Other Topics
SINGLE-CHAIN FV
VIRULENCE
Publication Status
Published
Coverage Spatial
England
Article Number
22939
Date Publish Online
2024-10-03