IL-15 adjuvanted multivalent vaccinia-based universal influenza vaccine requires CD4+ T cells for heterosubtypic protection

We present a novel vaccine that elicits protective immune responses against many different influenza viruses belonging to both group 1 and 2 lineages. The vaccine uses a live vaccinia virus that expresses multiple H5N1 influenza viral proteins and the cytokine IL-15 to stimulate the immune system. The vaccine was able to induce T-cell immune responses that recognize different influenza viruses and these immune responses were augmented when exposed to a challenge virus, resulting in protection against a lethal disease. Vaccine-induced CD4⁺ T cells that coordinate immune responses were found to be more important than CD8⁺ T cells in conferring protection. Our vaccine provides a promising strategy for universal protection against novel and emerging influenza viruses.