A "Prime And Deploy" Strategy For Universal Influenza Vaccine Targeting Nucleoprotein Induces Lung-Resident Memory Cd8 T Cells

Lung-resident memory T cells (T-RM) play an essential role in protecting against pulmonary virus infection. Parenteral administration of DNA vaccine is generally not sufficient to induce lung CD8 T-RM cells. This study investigates whether intramuscularly administered DNA vaccine expressing the nucleoprotein (NP) induces lung T-RM cells and protects against the influenza B virus. The results show that DNA vaccination poorly generates lung T-RM cells and massive secondary effector CD8 T cells entering the lungs after challenge infection do not offer sufficient protection. Nonetheless, intranasal administration of non-replicating adenovirus vector expressing no Ag following priming DNA vaccination deploys NP-specific CD8T T-RM cells in the lungs, which subsequently offers complete protection. This novel 'prime and deploy' strategy could be a promising regimen for a universal influenza vaccine targeting the conserved NP Ag.