Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses

Abstract

BackgroundThe sudden emergence of novel influenza viruses is a global public health concern. Conventional influenza vaccines targeting the highly variable surface glycoproteins hemagglutinin and neuraminidase must antigenically match the emerging strain to be effective. In contrast, “universal” vaccines targeting conserved viral components could be used regardless of viral strain or subtype. Previous approaches to universal vaccination have required protracted multi-dose immunizations. Here we evaluate a single dose universal vaccine strategy using recombinant adenoviruses (rAd) expressing the conserved influenza virus antigens matrix 2 and nucleoprotein.Methodology/Principal FindingsIn BALB/c mice, administration of rAd via the intranasal route was superior to intramuscular immunization for induction of mucosal responses and for protection against highly virulent H1N1, H3N2, or H5N1 influenza virus challenge. Mucosally vaccinated mice not only survived, but had little morbidity and reduced lung virus titers. Protection was observed as early as 2 weeks post-immunization, and lasted at least 10 months, as did antibodies and lung T cells with activated phenotypes. Virus-specific IgA correlated with but was not essential for protection, as demonstrated in studies with IgA-deficient animals.Conclusion/SignificanceMucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.

Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

“…In addition, due to the vital role of M2e in viral replication, it is of great interest to develop a universal vaccine based upon M2e, which is believed to be protective regardless of viral strain. [16][17][18] M2e is present in very low amounts on the influenza virus, so is unable to induce an immune response specifically to this epitope. Although M2e in virus-infected cells is abundant, 19 it cannot induce production of specific antibodies against M2e.…”

A recombinant protein containing highly conserved hemagglutinin residues 81-122 of influenza H5N1 induces strong humoral and mucosal immune responses

“…In addition to humoral immune responses, mucosal immunity characterized by secretory IgA antibody could also play an essential role in the protection against virus infection, especially those caused by influenza A virus, a mucosal pathogen infecting humans through the respiratory tract (35). Thus, an influenza vaccine potentially inducing ample mucosal immunity in the vaccinated hosts would be considered an important factor in developing effective influenza vaccines.…”

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

“…IFN-g and IL-4 ELISPOT assays were performed on splenocytes using mouse IFN-g and IL-4 ELISPOT kits (BD Biosciences, San Jose, CA) as previously described (32). Briefly, ELISPOT 96-well plates were coated with anti-mouse IFN-g and IL-4 capture Abs (5 mg/ml) in PBS at 4˚C overnight.…”