Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Echovirus 30 (E30), an Enterovirus B (EV-B) serotype, is a leading global cause of aseptic meningitis.
• E30 poses a significant threat to neonates, with no current vaccine or antiviral treatments available.

Purpose of the Study:

• To characterize two potent E30-specific monoclonal antibodies, 6C5 and 4B10.
• To elucidate the neutralizing mechanisms and structural basis of antibody-virus interactions for E30.

Main Methods:

• Characterization of monoclonal antibodies 6C5 and 4B10 against Echovirus 30.
• Structural analysis using high-resolution crystallography of antibody-virus complexes (E30-6C5-Fab and E30-4B10-Fab).
• Assessment of antibody efficacy in blocking viral attachment and uncoating receptor interactions.

Main Results:

• Monoclonal antibodies 6C5 and 4B10 potently neutralize E30 by blocking its interaction with CD55 and FcRn receptors.
• Combined administration of 6C5 and 4B10 demonstrated synergistic antiviral activity.
• Structural data revealed distinct epitopes targeted by 6C5 (north rim of the canyon) and 4B10 (in-canyon), highlighting antigenic variability within EV-B.

Conclusions:

• The characterized neutralizing antibodies provide a foundation for developing E30-specific therapeutics.
• Understanding the structural basis of neutralization and epitope variability is crucial for designing effective vaccines and broad-spectrum antivirals against EV-B infections.