Non-invasive universal influenza vaccine based on adenovirus vector

Current licensed influenza vaccines including injectable tetravalent inactivated virus (TIV) and nasal live attenuated influenza virus (LAIV) aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. The vaccines need to be reformulated every year to include new virus strains. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes including newly emerging strains. We generated recombinant adenovirus (rAd) vector encoding HA of H5 virus and M2e (rAdH5/M2e) as a vaccine against H5 and other subtypes. Since adenovirus and influenza virus share natural infection route, the respiratory tract, we proposed an intranasal (i.n.) administration of adenovirus-based vaccine as a non-invasive vaccination for safe and effective induction of cross-protective immunity. We found that single i.n. immunization of mice with the vaccine induced long-lasting protection against challenge with H5 or H1 virus subtypes. The cross-protection is associated with induction of Ab responses directed to conserved stalk HA and M2e that can be boosted upon repeated i.n. immunizations. Importantly, i.n. immunization with live vectored vaccine induced specific Ab responses in the gut. The findings support the development of non-invasive i.n. rAd vector encoding HA and M2e as a universal vaccine against different IAV subtypes and implicate nasal vectored vaccines for control of not only respiratory but also enteric pathogens.