Influenza viruses display antigenic drift necessitating development of updated vaccines each year. Misjudgment or absence of appropriate information can lead to design and production of vaccines with marginal ability to protect against the prevailing strains. Influenza also undergo genome reassansortment by co-infection of animal host cells with two different influenza viruses. Since there are influenza strains that infect birds, swine, horses and humans and since these host-adapted viruses have different antigenic components, genome reassortment can generate influenza strains that have never existed before. Consequently, such new reassortment viruses could cause an influenza pandemic, with potential to cause some 300 million world-wide deaths. The economic consequences of such a pandemic due to morbidity, health care delivery and in burying the deceased would be staggering. Since methods exist to generate such reassortment viruses in the laboratory or by willful co-infection of cells or animals, it must be appreciated that influenza could become a significant bioweapon. Another problem with current technology in making influenza vaccines is the reliance on using embryonated eggs that is time-consuming (taking four months), has low productivity and, most troublesome, cannot be used when needing to make vaccines with some avian influenza components. Our objective is to design, construct and evaluate a novel inexpensive rapidly modifiable vaccine for oral needle-free vaccination to deliver DNA vaccines and protective antigens/epitopes to induce protective immunity, including mucosal immunity, in children and adults to prevent infection by influenza viruses with avian and human antigenic components. In addition to relying on inducing protective immunity to HA antigens, we will thoroughly investigate the potential to induce a longer lasting cross-protective cellular immunity by delivery of conserved antigens containing T-cell epitopes. The vaccine delivery system employs attenuated Salmonella strains with special newly developed features to maximize colonization of lymphoid tissues and that display a regulated delayed lysis in vivo phenotype to release DNA vaccines encoding influenza hemagglutinin antigens in the cytosol of host cells and deliver protective antigens/epitopes to other tissues.
