A Fully Human Derived Monoclonal Antibody Provides Potent Pre- and Postexposure Protection Against Rabies Virus.

Area of Science:

• Virology
• Immunology
• Drug Development

Background:

• Rabies is a significant global health threat, especially in regions with limited access to postexposure prophylaxis (PEP).
• Current rabies immune globulin (RIG) treatments face challenges including supply shortages, inconsistent potency, and high costs.
• Recombinant monoclonal antibodies (mAbs) offer a potential solution due to their consistent quality and scalable production.

Purpose of the Study:

• To develop a fully human monoclonal antibody (mAb) targeting the rabies virus glycoprotein (RABV-G).
• To evaluate the efficacy of the developed mAb, H81L90, as a potential rabies postexposure prophylaxis (PEP).

Main Methods:

• Isolation of a fully human mAb (H81L90) from a phage-display library using PBMCs from vaccinated donors.
• Characterization of H81L90 binding affinity to RABV-G using surface plasmon resonance (SPR).
• Assessment of viral neutralization in cell-based assays and protective efficacy in a murine challenge model.

Main Results:

• H81L90 demonstrated strong, specific binding to native RABV-G with nanomolar affinity.
• The antibody efficiently neutralized the rabies virus in cell-based assays, inhibiting infection at low microgram concentrations.
• In mice, a single dose of H81L90 provided complete protection against rabies, even when administered postexposure, and reduced viral neuroinvasion.

Conclusions:

• H81L90 is a potent, fully human antibody with both preventive and postexposure prophylactic capabilities against rabies.
• This mAb shows potential as a next-generation biologic for rabies PEP, complementing or replacing existing RIG formulations.
• Further development of H81L90 is warranted to address limitations in current rabies treatment options.