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 CD8 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.