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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI065779-03
Application #
7174221
Study Section
Special Emphasis Panel (ZRG1-VMD (01))
Program Officer
Cho, David
Project Start
2005-08-16
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$712,024
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Miscellaneous
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Zhang, Xiangmin; Curtiss 3rd, Roy (2015) Efficient generation of influenza virus with a mouse RNA polymerase I-driven all-in-one plasmid. Virol J 12:95
Zhang, Xiangmin; Kong, Wei; Wanda, Soo-Young et al. (2015) Generation of influenza virus from avian cells infected by Salmonella carrying the viral genome. PLoS One 10:e0119041
Kong, Wei; Brovold, Matthew; Koeneman, Brian A et al. (2012) Turning self-destructing Salmonella into a universal DNA vaccine delivery platform. Proc Natl Acad Sci U S A 109:19414-9
Zhang, Xiangmin; Wanda, Soo-Young; Brenneman, Karen et al. (2011) Improving Salmonella vector with rec mutation to stabilize the DNA cargoes. BMC Microbiol 11:31
Ashraf, Shamaila; Kong, Wei; Wang, Shifeng et al. (2011) Protective cellular responses elicited by vaccination with influenza nucleoprotein delivered by a live recombinant attenuated Salmonella vaccine. Vaccine 29:3990-4002
Ameiss, Keith; Ashraf, Shamaila; Kong, Wei et al. (2010) Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype. Vaccine 28:6704-13
Zhang, Xiangmin; Kong, Wei; Ashraf, Shamaila et al. (2009) A one-plasmid system to generate influenza virus in cultured chicken cells for potential use in influenza vaccine. J Virol 83:9296-303