Development and characterization of influenza M2 ectodomain and/or hemagglutinin stalk-based dendritic cell-targeting vaccines

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 dendritic cell (DC)-targeting domain (E Delta M) fusion protein technology. The four copies of ectodomain matrix protein of influenza (tM2e) or M2e hemagglutinin stalk (HA stalk) peptides (HM2e) were fused with E Delta M to generate E Delta M-tM2e or E Delta M-HM2e, respectively. We demonstrated that E Delta M-HM2e- or E Delta M-tM2e-pseudotyped viral particles can efficiently target DC/macrophages in vitro and induced significantly high titers of anti-HA and/or anti-M2e antibodies in mice. Significantly, the recombinant vesicular stomatitis virus (rVSV)-E Delta M-tM2e and rVSV-E Delta M-HM2e vaccines mediated rapid and potent induction of M2 or/and HA antibodies in mice sera and mucosa. Importantly, vaccination of rVSV-E Delta M-tM2e or rVSV-E Delta M-HM2e protected mice from influenza H1N1 and H3N2 challenges. Taken together, our study suggests that rVSV-E Delta M-tM2e and rVSV-E Delta M-HM2e are promising candidates that may lead to the development of a universal vaccine against different influenza strains.