Universal influenza vaccine design: directing the antibody repertoire

Influenza infections are responsible for a large health and economic burden. Vaccination is the best strategy to reduce influenza-related disease burden, but current vaccines have limited breadth and need near-annual reformulation. Developing new influenza vaccines that provide broad and long-lasting protection is an important goal. This review represents an overview of the current knowledge of the universal vaccine approach that focuses on the induction of broadly neutralizing antibodies targeting the hemagglutinin (HA) stem of influenza viruses. Adjuvation of existing influenza vaccines has so far had limited effect on the induction of broadly neutralizing antibodies. HA stem-based immunogens that lack the immunodominant HA head have shown promising results in preclinical models, providing evidence that a universal influenza vaccine is within reach.