Figure 1.

Schematic diagram of broadly protective vaccine designs. (A) The three major steps to the creation of neutralizing epitopes-based vaccines. Major neutralizing epitopes on the protective antigen are identified with neutralizing antibodies. Next, the distribution of the identified epitopes is analyzed across multiple lineages for the selection of optimal vaccine strains or enable the modification of a vaccine antigen to best represent the neutralizing epitopes of antigenic subtypes. (B) Computationally optimized broadly reactive antigen (COBRA). The consensus sequences for each genotypic group are realigned to generate a secondary consensus, which is then aligned to obtain a single final consensus sequence based on conserved regions, designated as COBRA. (C) The ‘chimeric’ approach involves sequential vaccination with vaccines containing HA heads of distinct influenza subtypes grafted onto a conserved HA stalk for universal or broad protection against AIV subtypes. (D) The ‘mosaic’ approach replaces variable immunodominant antigenic sites with equivalents from other influenza HA subtypes to produce an immunogen with conserved epitopes in both the stalk and head domains.