Quantitative relationships between an influenza virus and neutralizing antibody

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Influenza virus neutralization by antibodies is crucial for antiviral immunity.
• Understanding the stoichiometry of antibody binding to viral surface proteins is essential for vaccine design and therapeutic strategies.

Purpose of the Study:

• To quantitatively determine the maximum number of antibody molecules that can bind to influenza virus haemagglutinin (HA) spikes.
• To identify the minimum number of antibodies required for effective influenza virus neutralization.
• To elucidate the mechanism underlying influenza virus neutralization kinetics.

Main Methods:

• Quantitative analysis of antibody-virus interactions using radiolabeled immunoglobulins.
• Measurement of antibody binding to native influenza A/FPV/Rostock/34 (H7N1) particles.
• Assessment of virus infectivity neutralization.
• Electron microscopy to support binding data.

Main Results:

• Approximately one IgG molecule binds per HA spike under antibody saturation conditions.
• Around 70 molecules of monoclonal IgGs were bound per virus particle for 63% infectivity neutralization.
• Neutralization kinetics were predominantly single-hit, occasionally two-hit under specific conditions.

Conclusions:

• Neutralization is proposed to occur via antibody binding to a minority of
• neutralization relevant
• HA spikes, distinguished by their transmembrane interactions.
• This finding reconciles the observed binding stoichiometry with neutralization kinetics.