• influenza;
  • neutralizing antibodies;
  • vaccine

Although seasonal influenza vaccines play a valuable role in reducing the spread of virus at the population level, ongoing viral evolution to evade immune responses remains problematic. No current vaccines elicit enduring protection in the face of emerging and re-emerging influenza viruses that are rapidly undergoing antigenic drift. Eliciting broadly cross-neutralizing antibody (nAb) responses against influenza virus is a crucial goal for seasonal and pandemic influenza vaccine preparation. Recent three-dimensional structure information obtained from crystallization of influenza antigens in complex with nAbs has provided a framework for interpreting antibody-based viral neutralization that should aid in the design of vaccine immunogens. Here, we will review current knowledge of the structure-based mechanisms contributing to the neutralization and neutralization escape of influenza viruses. We will also explore the potential for this structure-based approach to overcome the obstacles in developing the highly desired “universal” influenza vaccine.