title: A candidate dual vaccine against influenza and noroviruses.
abstract: The extracellular domain of the matrix protein 2 (M2e) of influenza viruses is highly conserved among all influenza A subtypes, making it a suitable target for a universal influenza vaccine. In this study, we demonstrated an enhanced immune response and protection of a chimeric M2e vaccine against influenza A viruses using our newly developed vaccine platform, the norovirus P particle, to present the M2e peptide. The 23-amino acid peptide was inserted into one of the surface loops of the P protein, resulting in 24 copies of M2e presented on each P particle. Significantly (P<0.001) increased antibody responses to M2e were observed in mice immunized with the P particle-M2e chimera compared with those immunized with the free M2e peptides. Mice immunized with the P particle-M2e vaccine were fully protected (100% survived) against lethal challenge of a mouse adapted human influenza virus PR8 (H1N1), while only low survival rates (<12.5%) were found in mice immunized with the free M2e peptides or wild type P particle. In addition, the mouse sera collected after immunization with the P particle-M2e vaccine were able to block the binding of norovirus virus-like particle and P particle to histo-blood group antigen receptors. These results suggest that the P particle-M2e chimera can be used as dual vaccine against both noroviruses and influenza viruses.
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Chao
authors.initials: C
authors.lastname: Wei
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhong
authors.forename: Leyi
authors.initials: L
authors.lastname: Wang
authors.forename: Monica
authors.initials: M
authors.lastname: McNeal
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D029322:Norovirus / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000517:prevention & control; D016019:Survival Analysis; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D036022:Capsid Proteins; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins