title: A novel subnucleocapsid nanoplatform for mucosal vaccination against influenza virus that targets the ectodomain of matrix protein 2.
abstract: In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.
authors.affiliation: INRA, UR0892 Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Hervé
authors.forename: Mariam
authors.initials: M
authors.lastname: Raliou
authors.forename: Christiane
authors.initials: C
authors.lastname: Bourdieu
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubuquoy
authors.forename: Agnès
authors.initials: A
authors.lastname: Petit-Camurdan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertho
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevalier
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009092:Mucous Membrane / Q000276:immunology*; D049329:Nanostructures; D019251:Nucleocapsid; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins