title: Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype.
abstract: The use of live recombinant attenuated Salmonella vaccines (RASV) is a promising approach for controlling infections by multiple pathogens. The highly conserved extracellular domain of the influenza M2 protein (M2e) has been shown to provide broad spectrum protection against multiple influenza subtypes sharing similar M2e sequences. An M2e epitope common to a number of avian influenza subtypes was inserted into the core antigen of woodchuck hepatitis virus and expressed in two different recombinant attenuated Salmonella Typhimurium strains. One strain was attenuated via deletion of the cya and crp genes. The second strain was engineered to exhibit a programmed delayed lysis phenotype. Both strains were able to produce both monomeric fusion proteins and fully assembled core particles. Mice orally immunized with the strain exhibiting delayed lysis induced significantly greater antibody titers than the Δcya Δcrp strain and provided moderate protection against weight loss to a low level challenge with the influenza strain A/WSN/33 modified to express the M2e sequence common to avian viruses. Further studies indicated that the Salmonella expressed core antigen induced comparable antibody levels to the purified core antigen injected with an alum adjuvant and that both are able to reduce viral replication in the lungs. To our knowledge this is the first report demonstrating Salmonella-mediated delivery of influenza virus M2e protein in a mammalian host to induce a protective immune response against viral challenge.
authors.affiliation: The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Ameiss
authors.forename: Shamaila
authors.initials: S
authors.lastname: Ashraf
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Andrew
authors.initials: A
authors.lastname: Pekosz
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Milich
authors.forename: Jean-Noel
authors.initials: JN
authors.lastname: Billaud
authors.forename: Roy
authors.initials: R
authors.lastname: Curtiss
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D005260:Female; D017919:Hepatitis B Virus, Woodchuck / Q000276:immunology; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins