Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
Caroline Gravel,
Abenaya Muralidharan,
Amparo Duran,
Adrian Zetner,
Annabelle Pfeifle,
Wanyue Zhang,
Anwar Hashem,
Levi Tamming,
Aaron Farnsworth,
Hugues Loemba,
Wangxue Chen,
Florian Krammer,
David Safronetz,
Jingxin Cao,
Lisheng Wang,
Simon Sauve,
Michael Rosu-Myles,
Gary Van Domselaar,
Xuguang Li
Affiliations
Caroline Gravel
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada
Abenaya Muralidharan
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada
Amparo Duran
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada
Adrian Zetner
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
Annabelle Pfeifle
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Wanyue Zhang
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Anwar Hashem
Immunotherapy Unit, Department of Medical Microbiology and Parasitology, Faculty of Medicine and Vaccines, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
Levi Tamming
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Aaron Farnsworth
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada
Hugues Loemba
Montfort Hospital and Faculty of Medicine, University of Ottawa, Ottawa, On, Canada
Wangxue Chen
Human Health Therapeutics Research Center, National Research Council of Canada, Ottawa, ON, Canada
Florian Krammer
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
David Safronetz
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
Jingxin Cao
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
Lisheng Wang
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Simon Sauve
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada
Michael Rosu-Myles
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
Gary Van Domselaar
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Corresponding author
Xuguang Li
Centre for Biologics Evaluation, Biologic and Radiopharmaceutical Drugs Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Corresponding author
Summary: A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.
