AI Article Synopsis
- The objective of this study was to explore the use of monoclonal antibodies (mAbs) as a safer and more effective alternative to traditional rabies immunoglobulin (RIG) for post-exposure rabies treatment.
- Researchers developed a mAb combination called CRM25, made from two non-competing human mAbs, RM02 and RM05, which target different parts of the rabies virus.
- Results showed that CRM25 effectively neutralized various rabies virus strains and demonstrated protective abilities in animal models, suggesting it could be a promising candidate for rabies treatment.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.ijantimicag.2024.107383 | DOI Listing |
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