Brian J Ward1, Nathalie Landry2, Sonia Trépanier3, Geneviève Mercier4, Michèle Dargis5, Manon Couture6, Marc-André D'Aoust7, Louis-P Vézina8. 1. Research Institute of the McGill University Health Center, Montreal, QC, Canada. Electronic address: brian.ward@mcgill.ca. 2. Medicago Inc. , Quebec, QC, Canada. Electronic address: landryn@medicago.com. 3. Medicago Inc. , Quebec, QC, Canada. Electronic address: trepaniers@medicago.com. 4. Medicago Inc. , Quebec, QC, Canada. Electronic address: mercierg@medicago.com. 5. Medicago Inc. , Quebec, QC, Canada. Electronic address: dargism@medicago.com. 6. Medicago Inc. , Quebec, QC, Canada. Electronic address: couturem@medicago.com. 7. Medicago Inc. , Quebec, QC, Canada. Electronic address: daoustma@medicago.com. 8. Medicago Inc. , Quebec, QC, Canada. Electronic address: vezinalp@medicago.com.
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 eitherone (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. CONCLUSION: 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.
RCT Entities:
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. CONCLUSION: 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: Teen-Lee Pua; Xiao Ying Chan; Hwei-San Loh; Abdul Rahman Omar; Vidadi Yusibov; Konstantin Musiychuk; Alexandra C Hall; Megan V Coffin; Yoko Shoji; Jessica A Chichester; Hong Bi; Stephen J Streatfield Journal: Hum Vaccin Immunother Date: 2016-12-08 Impact factor: 3.452
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