title: M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.
abstract: The ectodomain of influenza A matrix protein 2 (M2e) is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs). We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+) T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2) or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
authors.forename: Lorena Itatí
authors.initials: LI
authors.lastname: Ibañez
authors.forename: Kenny
authors.initials: K
authors.lastname: Roose
authors.forename: Marina
authors.initials: M
authors.lastname: De Filette
authors.forename: Michael
authors.initials: M
authors.lastname: Schotsaert
authors.forename: Jessica
authors.initials: J
authors.lastname: De Sloovere
authors.forename: Stefan
authors.initials: S
authors.lastname: Roels
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pollard
authors.forename: Bert
authors.initials: B
authors.lastname: Schepens
authors.forename: Johan
authors.initials: J
authors.lastname: Grooten
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
mesh_terms: D056704:Adaptive Immunity; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D012313:RNA / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination; D058425:Vaccines, Virus-Like Particle / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D007252:Influenza Vaccines; C509609:M2e-HBc influenza vaccine; D053594:Myeloid Differentiation Factor 88; D058425:Vaccines, Virus-Like Particle; D012313:RNA