Universal Influenza Vaccine Approaches Using Full-Length or Head-Only Hemagglutinin Proteins

There is currently an unmet need to develop an effective broadly reactive or universal vaccine against influenza viruses capable of conferring protection against both seasonal and prepandemic strains. Influenza vaccines elicit immune responses that are protective against antigenically similar viruses within a subtype. These vaccines elicit antibodies that target the surface viral glycoproteins hemagglutinin and neuraminidase. If there is an antigenic mismatch between these proteins in the influenza vaccines and cocirculating influenza isolates, there is a decrease in the vaccine effectiveness in vaccinated persons. Various novel influenza vaccine candidates are being evaluated in animal studies and clinical human trials. This article focuses on the advantages and potential shortcomings of broadly reactive or universal vaccine candidates based on the hemagglutinin globular head and the thoughts about using this antigen as the basis for future influenza vaccine strategies.