Development and characterization of influenza M2 ectodomain and/or HA stalk-based DC-targeting vaccines for different influenza infections

Abstract

A universal influenza vaccine is required for broad protection against influenza infection. Here, we revealed the efficacy of novel influenza vaccine candidates based on Ebola glycoprotein (EboGP) DC-targeting domain (E{Delta}M) fusion protein technology. We fused influenza hemagglutinin stalk (HAcs) and extracellular matrix protein (M2e) or four copies of M2e (referred to as tetra M2e (tM2e)) with E{Delta}M to generate E{Delta}M-HM2e or E{Delta}M-tM2e, respectively, and revealed that E{Delta}M facilitates DC/macrophage targeting in vitro. In a mouse study, E{Delta}M-HM2e- or E{Delta}M-tM2e-pseudotyped viral particles (PVPs) induced significantly higher titers of anti-HA and/or anti-M2e antibodies. We also developed recombinant vesicular stomatitis virus (rVSV)-E{Delta}M-HM2e and rVSV-E{Delta}M-tM2e vaccines that resulted in rapid and potent induction of HA and/or M2 antibodies in mouse sera and mucosa. Importantly, vaccination protects mice from influenza H1N1 and H3N2 challenges. Taken together, our study suggests that recombinant rVSV-E{Delta}M-HM2e and rVSV-E{Delta}M-tM2e are efficacious and protective universal vaccines against influenza.