A Humanized Anti-gD Broadly Neutralizing Antibody Confers Complete Post-Exposure Protection against Pseudorabies...

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Pseudorabies virus (PRV), an alpha-herpesvirus, poses a significant zoonotic threat.
• PRV infection in humans can cause severe encephalitis and endophthalmitis with high mortality.
• Currently, no effective treatments exist for human PRV infections.

Purpose of the Study:

• To identify and characterize a broadly neutralizing antibody against PRV.
• To investigate the therapeutic potential of this antibody for human PRV infection.

Main Methods:

• Isolation and characterization of a monoclonal antibody (6F7) targeting PRV glycoprotein D (gD).
• Mechanistic studies to determine the antibody's mechanism of action (viral attachment, internalization, fusion, cell-to-cell spread).
• In vivo efficacy studies using a humanized antibody version in a lethal PRV mouse model.

Main Results:

• The 6F7 antibody broadly neutralizes all tested PRV lineages by blocking viral envelope and cell membrane fusion.
• 6F7 inhibits PRV replication and cell-to-cell spread by preventing gD-Nectin-1 interaction.
• A humanized 6F7 antibody conferred complete protection against lethal PRV challenge and prevented latency in mice.

Conclusions:

• The broadly neutralizing antibody 6F7 is a potent inhibitor of PRV.
• Humanized 6F7 represents a promising therapeutic candidate for treating human PRV infections.