Figure 3.

HA-specific approaches for universal influenza vaccines: (A) Sequential immunization with chimeric HA head: The strategy is based on the multiple HAs to use an identical stem domain with different exotic head domains. The robust immune response against the HA stem is generated by sequential administration. (B) Sequential immunization with mosaic HA head: The major immunogenic sites of the head domain are replaced with the sequences from exotic viral strains leading to an enhanced immune response against the HA stem domain. (C) Hyperglycosylation of HA head: The HA hyperglycosylation shields the antigenic sites from recognition by neutralizing antibodies. It may lead to better recognition of the HA stem domain-specific epitopes. (D) Consensus HA sequence: The consensus HA sequence is generated by aligning HA protein sequences from the database. The HA consensus protein may provide broad protection. (E) Micro-consensus HA sequence and COBRA: Micro-consensus sequences are based on the consensus sequences from each branch of a phylogenetic tree. The cocktail administration can provide better efficacy in highly diverse HA populations. COBRA sequence is generated by multiple rounds of the consensus sequence procedure, thereby reducing the sampling bias.