Developing a human monoclonal antibody combination CRM25 to prevent rabies after exposure.

Autor: Long C; Division of Monoclonal Antibody Products, National Institutes for Food and Drug Control, State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, China., Wang W; Center for Drug Evaluation, National Medical Products Administration, Beijing, China., Du J; Division of Monoclonal Antibody Products, National Institutes for Food and Drug Control, State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, China., Xu G; Division of Monoclonal Antibody Products, National Institutes for Food and Drug Control, State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, China., Yu C; Division of Monoclonal Antibody Products, National Institutes for Food and Drug Control, State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, China. Electronic address: yuchuanfei@126.com., Wang L; Division of Monoclonal Antibody Products, National Institutes for Food and Drug Control, State Key Laboratory of Drug Regulatory Science, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, China. Electronic address: wanglan@nifdc.org.cn.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 Dec; Vol. 64 (6), pp. 107383. Date of Electronic Publication: 2024 Nov 13.
DOI: 10.1016/j.ijantimicag.2024.107383
Abstrakt: Objective: Immunization against rabies post-exposure prophylaxis requires passive immunization with either monoclonal antibody (mAb) or blood-derived rabies immunoglobin (RIG). Currently, replacing traditional RIG with emerging mAb or mAb combinations is highly recommended due to the limited supply and potential safety risks of RIG.
Methods: We developed a mAb combination named CRM25 by combining two human mAbs, RM02 and RM05, at a 1:1 mass ratio.
Results: RM02 and RM05 were non-competing and non-overlapping mAbs targeting epitopes I and III, respectively. K226 and G229 were found to be the critical amino acid sites for RM02 neutralization, but the mutant I338T displayed decreased susceptibility to RM05 neutralization. Notably, CRM25 was capable of cross-neutralizing rabies virus (RABV) strains containing K226M or I338T mutations. CRM25 additionally showed an inhibitory effect on the infection of all tested common RABVs and non-RABV phylogroup I lyssaviruses. CRM25 not only exhibited neutralizing activity but also exhibited antiviral effects via Fc-mediated effector functions. Importantly, CRM25 was comparable to human RIG in terms of its capacity to protect Syrian golden hamsters from lethal RABV challenges.
Conclusions: These findings promote more thorough research on CRM25's antiviral properties in cells and in vivo to enhance its clinical applicability and suggest that it may be a viable candidate medication for rabies post-exposure prophylaxis.
(Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
Databáze: MEDLINE
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