title: Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus.
abstract: Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Miriam
authors.initials: M
authors.lastname: Klausberger
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.|Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Tscheliessnig
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Silke
authors.initials: S
authors.lastname: Neff
authors.affiliation: Faculty of Life Sciences, University of Vienna, Vienna, Austria.|Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Raffael
authors.initials: R
authors.lastname: Nachbagauer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Teddy John
authors.initials: TJ
authors.lastname: Wohlbold
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Wilde
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Palmberger
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Alois
authors.initials: A
authors.lastname: Jungbauer
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, Vienna, Austria.
authors.forename: Reingard
authors.initials: R
authors.lastname: Grabherr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D010446:Peptide Fragments