title: Hexon-modified recombinant E1-deleted adenovirus vectors as dual specificity vaccine carriers for influenza virus.
abstract: To determine if an ordered and repetitive display of an epitope promoted induction of superior antibody responses, we compared B-cell responses to an influenza A virus epitope that was either encoded as a transgene by an adenovirus (Ad) vector or expressed on the vector's surface. To this end, we constructed a panel of influenza A virus vaccines based on chimpanzee-derived replication-defective adenovirus (AdC) vectors of serotype SAd-V25 also called AdC68. AdC68 vectors were modified to express a linear B-cell epitope of the ectodomain of matrix 2 (M2e) within variable regions 1 (VR1) or 4 (VR4) of the adenovirus hexon. Additional vectors with wild-type or M2e-modified hexon encoded M2e fused to the influenza A virus nucleoprotein (NP) as a transgene product. Hexon-modified vectors were tested for immunogenicity and efficacy in mice in comparison to vectors with native hexon expressing the M2e-NP fusion protein. Upon priming, vectors expressing M2e within VR1 of hexon induced M2e-specific antibody responses of higher magnitude and avidity than those carrying M2e within VR4 or vectors expressing the M2e as part of a transgene product. CD8(+) T-cell responses to the transgenic NP were comparable between vectors. M2e-specific antibody responses could be boosted by a second dose of the VR1 hexon-modified vector but not by repeated immunization with the VR4 hexon-modified vector.
authors.affiliation: The Wistar Institute, Philadelphia, PA, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
authors.forename: Te-Lang
authors.initials: TL
authors.lastname: Wu
authors.forename: Kristel L
authors.initials: KL
authors.lastname: Emmer
authors.forename: Raj
authors.initials: R
authors.lastname: Kurupati
authors.forename: Steven
authors.initials: S
authors.lastname: Tuyishime
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wynetta
authors.initials: W
authors.lastname: Giles-Davis
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhiquan
authors.initials: Z
authors.lastname: Xiang
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Ratcliffe
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015316:Genetic Therapy; D005822:Genetic Vectors; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012680:Sensitivity and Specificity; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D000086082:Viroporin Proteins
chemical_list: D018985:Epitopes, B-Lymphocyte; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C048842:NP protein, Influenza A virus