title: Conserved synthetic peptides from the hemagglutinin of influenza viruses induce broad humoral and T-cell responses in a pig model.
abstract: Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines à la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations.
authors: Centre de Recerca en Sanitat Animal, Universitat Autònoma de Barcelona-Institut de Recerca i Tecnologia Agroalimentària, Campus de la Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain. julia.vergara@cresa.uab.cat
authors: Júlia
authors: J
authors: Vergara-Alert
authors: Jordi M
authors: JM
authors: Argilaguet
authors: Núria
authors: N
authors: Busquets
authors: Maria
authors: M
authors: Ballester
authors: Gerard E
authors: GE
authors: Martín-Valls
authors: Raquel
authors: R
authors: Rivas
authors: Sergio
authors: S
authors: López-Soria
authors: David
authors: D
authors: Solanes
authors: Natàlia
authors: N
authors: Majó
authors: Joaquim
authors: J
authors: Segalés
authors: Veljko
authors: V
authors: Veljkovic
authors: Fernando
authors: F
authors: Rodríguez
authors: Ayub
authors: A
authors: Darji
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000918:Antibody Specificity; D018893:Bronchoalveolar Lavage; D017124:Conserved Sequence; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology / Q000502:physiology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D058873:Pandemics / Q000517:prevention & control; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D013045:Species Specificity; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D014765:Viral Vaccines