title: Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.
abstract: In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against this potentially pandemic virus.
authors.affiliation: Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada; Research Institute of the McGill University Health Center, Montreal, QC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Pillet
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Racine
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Nfon
authors.affiliation: Research Institute of the McGill University Health Center, Montreal, QC, Canada.
authors.forename: T Z
authors.initials: TZ
authors.lastname: Di Lenardo
authors.affiliation: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada; Department of Immunology, University of Manitoba, MB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Babiuk
authors.affiliation: Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada.
authors.forename: B J
authors.initials: BJ
authors.lastname: Ward
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Immunology, University of Manitoba, MB, Canada; Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: G P
authors.initials: GP
authors.lastname: Kobinger
authors.affiliation: Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada. Electronic address: landryn@medicago.com.
authors.forename: N
authors.initials: N
authors.lastname: Landry
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D007115:Immunization Schedule; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007273:Injections, Intramuscular; D008168:Lung / Q000821:virology; D008297:Male; D008807:Mice, Inbred BALB C; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000517:prevention & control; D010919:Placebos / Q000008:administration & dosage; D030821:Plants, Genetically Modified; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014026:Nicotiana; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D010919:Placebos; D011994:Recombinant Proteins; D058425:Vaccines, Virus-Like Particle; C109963:hemagglutinin, avian influenza A virus
keywords: Ferrets; H7N9; Immunogenicity; Influenza A; Mice; NICOTIANA benthamiana; Plant-made vaccine; Virus-like particle