title: Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens.
abstract: Cell-mediated immunity plays a major role in long-lived, cross-reactive protection against influenza virus. We measured long-term poly-functional and cross-reactive T cell responses to influenza hemagglutinin (HA) elicited by a new plant-made Virus-Like Particle (VLP) vaccine targeting either H1N1 A/California/7/09 (H1) or H5N1 A/Indonesia/5/05 (H5). In two independent clinical trials, we characterized the CD4(+) and CD8(+) T cell homotypic and heterotypic responses 6 months after different vaccination regimens. Responses of VLP-vaccinated subjects were compared with placebo and/or a commercial trivalent inactivated vaccine (TIV:Fluzone™) recipients. Both H1 and H5 VLP vaccines elicited significantly greater poly-functional CD4(+) T cell responses than placebo and TIV. Poly-functional CD8(+) T cell responses were also observed after H1 VLP vaccination. Our results show that plant-made HA VLP vaccines elicit both strong antibody responses and poly-functional, cross-reactive memory T cells that persist for at least 6 months after vaccination.
authors.affiliation: Medicago inc., 1020 Route de l'Église, Bureau 600, Québec, Qc G1V 3V9, Canada. Electronic address: landryn@medicago.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Landry
authors.affiliation: Medicago inc., 1020 Route de l'Église, Bureau 600, Québec, Qc G1V 3V9, Canada; Research Institute of the McGill University Health Center, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Qc H3G 1A4, Canada. Electronic address: pillets@medicago.com.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pillet
authors.affiliation: ImmuneCarta, 201 President-Kennedy, Suite PK-3900, Montreal, Qc H2X 3Y7, Canada. Electronic address: dfavre@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Favre
authors.affiliation: ImmuneCarta, 201 President-Kennedy, Suite PK-3900, Montreal, Qc H2X 3Y7, Canada. Electronic address: jpoulin@immunecarta.com.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Poulin
authors.affiliation: Medicago inc., 1020 Route de l'Église, Bureau 600, Québec, Qc G1V 3V9, Canada. Electronic address: trepaniers@medicago.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Trépanier
authors.affiliation: ImmuneCarta, 201 President-Kennedy, Suite PK-3900, Montreal, Qc H2X 3Y7, Canada. Electronic address: byassine@immunecarta.com.
authors.forename: Bader
authors.initials: B
authors.lastname: Yassine-Diab
authors.affiliation: Research Institute of the McGill University Health Center, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Qc H3G 1A4, Canada. Electronic address: brian.ward@mcgill.ca.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D015415:Biomarkers; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000502:physiology*; D014026:Nicotiana / Q000166:cytology* / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D015415:Biomarkers; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: Cell-mediated immunity; Influenza; Long-term memory response; Nicotiana benthamiana; Vaccine; Virus-like particle