title: Human antibody response to N-glycans present on plant-made influenza virus-like particle (VLP) vaccines.
abstract: BACKGROUND
  Plant-made biotherapeutics are gathering momentum and some plant glycoproteins are allergens. Glycans with core β1-2xylose and α1,3fucose motifs and antennae terminated by mannose residues (e.g.: MMXF) are found on several plant allergens and can cross-react with glyco-epitopes from other sources. To date, reactivity to these cross-reactive determinants has not been associated with clinical symptoms.
  
  
  OBJECTIVE
  We produced VLP vaccines bearing the hemagglutinin(HA) of H5(A/Indonesia/5/05) or H1(A/California/07/09) influenza viruses by transfection of Nicotiana benthamiana. Subjects enrolled in Phase I/II trials were followed for evidence of allergy/hypersensitivity and development of antibodies against plant glyco-epitopes.
  
  
  METHODS
  A total of 280/349 subjects received either one (H1) or 2 doses (H5) of vaccine (5-45 μg of HA/dose) intramuscularly including 40 with pre-existing plant allergies. Subjects were monitored for 6 months. IgG and IgE to plant glyco-epitopes were measured by ELISA using corn-/egg-derived avidin and bromelain as target antigens.
  
  
  RESULTS
  No subject developed allergic/hypersensitivity symptoms. Some (34%) developed transient IgG and, in some cases IgE, to plant glyco-epitopes but no subject mounted an IgE response to the MMXF motif. Antibodies returned to baseline by 6 months in most subjects.
  
  
  CONCLUSIONS
  VLP vaccines bearing influenza HA glycoproteins can elicit transient IgG and, in some cases, IgE responses that are not associated with either the development or worsening of allergic/hypersensitivity symptoms.
authors.affiliation: Research Institute of the McGill University Health Center, Montreal, QC, Canada. Electronic address: brian.ward@mcgill.ca.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: landryn@medicago.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Landry
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: trepaniers@medicago.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Trépanier
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: mercierg@medicago.com.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Mercier
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: dargism@medicago.com.
authors.forename: Michèle
authors.initials: M
authors.lastname: Dargis
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: couturem@medicago.com.
authors.forename: Manon
authors.initials: M
authors.lastname: Couture
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: daoustma@medicago.com.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: D'Aoust
authors.affiliation: Medicago Inc. , Quebec, QC, Canada. Electronic address: vezinalp@medicago.com.
authors.forename: Louis-P
authors.initials: LP
authors.lastname: Vézina
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000917:Antibody Formation; D003429:Cross Reactions / Q000276:immunology*; D004311:Double-Blind Method; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D009980:Influenza A virus; D007252:Influenza Vaccines / Q000096:biosynthesis / Q000276:immunology*; D008875:Middle Aged; D011134:Polysaccharides / Q000276:immunology*; D014026:Nicotiana / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000096:biosynthesis / Q000276:immunology*; D055815:Young Adult; D003313:Zea mays / Q000276:immunology
chemical_list: D000485:Allergens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011134:Polysaccharides; D058425:Vaccines, Virus-Like Particle; D007073:Immunoglobulin E
keywords: Allergy; Bromelain assay; CCDs; Cross-reactive carbohydrate determinants; Humoral response; IgE; IgG; Influenza A virus; Plant-made vaccines; Plant-specific glycans