To dream the impossible dream: universal influenza vaccination

• Influenza A virus vaccines must become more effective.
• Recent advances in basic immunology and immunology offer new strategies for improved vaccines.
• The stem region of the viral hemagglutinin is the most promising target for vaccines that resist antigenic drift.
• Many basic questions must be answered to rationally develop optimized vaccines.

Year in and year out, influenza viruses exact a deadly and expensive toll on humanity. Current vaccines simply do not keep pace with viral immune evasion, providing partial protection, at best, among various age groups. A quantum leap in understanding the basic principles of the adaptive and innate immune responses to influenza viruses offers the opportunity to develop vaccines that forestall, and potentially ultimately defeat, influenza virus antigenic variation.