title: A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults.
abstract: Recent issues regarding efficacy of influenza vaccines have re-emphasized the need of new approaches to face this major public health issue. In a phase 1-2 clinical trial, healthy adults received one intramuscular dose of a seasonal influenza plant-based quadrivalent virus-like particle (QVLP) vaccine or placebo. The hemagglutination inhibition (HI) titers met all the European licensure criteria for the type A influenza strains at the 3μg/strain dose and for all four strains at the higher dosages 21days after immunization. High HI titers were maintained for most of the strains 6months after vaccination. QVLP vaccine induced a substantial and sustained increase of hemagglutinin-specific polyfunctional CD4 T cells, mainly transitional memory and TEMRA effector IFN-γ(+) CD4 T cells. A T cells cross-reactive response was also observed against A/Hong-Kong/1/1968 H3N2 and B/Massachusetts/2/2012. Plant-based QVLP offers an attractive alternative manufacturing method for producing effective and HA-strain matching seasonal influenza vaccines.
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9; Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, QC, Canada, H3H 2R9.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pillet
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9.
authors.forename: Éric
authors.initials: É
authors.lastname: Aubin
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9.
authors.forename: Sonia
authors.initials: S
authors.lastname: Trépanier
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9.
authors.forename: Diane
authors.initials: D
authors.lastname: Bussière
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9.
authors.forename: Michèle
authors.initials: M
authors.lastname: Dargis
authors.affiliation: ImmuneCarta, 201 Avenue du Président-Kennedy, Montreal, QC, Canada, H2X 3Y7.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Poulin
authors.affiliation: ImmuneCarta, 201 Avenue du Président-Kennedy, Montreal, QC, Canada, H2X 3Y7.
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.affiliation: Research Institute of the McGill University Health Centre, 2155 Guy Street, 5th Floor, Montreal, QC, Canada, H3H 2R9.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.affiliation: Medicago Inc., 1020 route de l'Église office 600, Québec, QC, Canada, G1V 3V9. Electronic address: Landryn@medicago.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Landry
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005221:Fatigue / Q000209:etiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014026:Nicotiana / Q000235:genetics; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D007371:Interferon-gamma
keywords: Cell-mediated immunity; Cross-reactive response; Nicotiana benthamiana; Plant-derived quadrivalent influenza vaccine; Safety and immunogenicity; Virus-like particles