Modern influenza vaccines are very effective against the strains they are composed of. However, variations between flu strains easily bypasses the induced immunity, rendering the vaccine outdated by the time the next flu season comes around. Current research into a “universal” influenza vaccine that can elicit a broadly protective response from the immune system has made great progress. Most methods are designed to induce broadly neutralizing antibodies to conserved sequences within surface glycoproteins. These methods can be adapted to induce broad cellular immunity as well. Memory to conserved sequences grants the immune system protection against divergent strains of influenza that share these sequences of conservation. The strategies explored in this review have the potential to become the next breakthrough in viral pathogen vaccination.

Discussed are methods including direct conserved antigen administration, modified glycoprotein vaccines, and sequential vaccination designs for DNA vaccines and antigenically similar constructs. Additionally, designs adapted from related viral pathogen studies including virus-like particle vaccines, COBRA vaccines, and immunity from vectored immunoprophylaxis. The strategies reported have shown to be effective in animal studies, however, continued experimentation is necessary before clinical trials.