The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection.

Mucosal vaccination requires effective and safe adjuvants. We have evaluated the non-toxic adjuvant CTA1-DD for mucosal vaccination against influenza. CTA1-DD contains the enzymatically active CTA1 subunit of cholera toxin (CT) genetically fused to a gene encoding a dimer of the D-fragment from Staphylococcus aureus protein A. CTA1-DD only binds to Ig-receptor carrying cells of the immune system. Nasal administration of the universal influenza vaccine M2e-HBc in combination with CTA1-DD completely protected mice from a potentially lethal infection and significantly reduced morbidity. Sera of mice immunized with M2e-HBc + CTA1-DD revealed IgG subclass profiles consistent with an enhanced Th1-type immunity. When the vaccine was administered intraperitoneally, the adjuvant improved the M2e antibody titer in circulation, but did not significantly reduce the morbidity.