A broadly protective antibody targeting gammaherpesvirus gB

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Gammaherpesviruses are oncogenic viruses causing significant human and animal diseases.
• No specific antiviral agents are currently available for the entire gammaherpesvirus family.
• Glycoprotein B (gB) is crucial for viral entry and a potential target for broad-spectrum vaccines.

Purpose of the Study:

• To elucidate the molecular basis for broad gammaherpesvirus binding and neutralization by an antibody.
• To assess the therapeutic potential of this antibody against authentic gammaherpesvirus challenges.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) to determine antibody-epitope interactions.
• In vivo efficacy studies in immune-competent mice, non-human primates, and humanized mice.
• Testing against murine, rhesus, and human gammaherpesviruses.

Main Results:

• The antibody Fab5 binds to a conserved and vulnerable epitope on gammaherpesvirus gB.
• Fab5 demonstrated broad neutralization across different gammaherpesvirus species.
• Effective protection was observed in multiple animal models against authentic virus challenges.

Conclusions:

• Fab5 represents a cross-genus antibody with broad reactivity against gammaherpesvirus.
• The findings provide insights into common mechanisms of gammaherpesvirus infection.
• This study facilitates the development of broad-spectrum vaccines against gammaherpesvirus.