title: Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets.
abstract: Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: S K
authors.initials: SK
authors.lastname: Rosendahl Huber
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
authors.forename: M G M
authors.initials: MG
authors.lastname: Camps
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: R H J
authors.initials: RH
authors.lastname: Jacobi
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Mouthaan
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Dijken
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Beek
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: de Jonge
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016208:Databases, Factual; D004285:Dogs; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005289:Ferrets; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D022223:Vaccines, Subunit / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins