title: Development of an Ad5H3 Chimera Using the "Antigen Capsid-Incorporation" Strategy for an Alternative Vaccination Approach.
abstract: BACKGROUND
  Adenovirus type 5 (Ad5) achieved success as a conventional transgene vaccine vector in preclinical trials, however; achieved poor efficiency in some of the clinical trials, due to the major hurdle associated with Ad5 pre-existing immunity (PEI) in the majority of the human population.
  
  
  OBJECTIVE
  We sought to generate Ad5-based chimeras to assess their capabilities to bypass this bottleneck and to induce antigen-specific humoral immune response.
  
  
  METHODS
  A His6 tag was incorporated into the hypervariable region 2 (HVR2) of hexon3 (H3) capsid protein using the "Antigen Capsid-Incorporation" strategy. This lead to the construction of a viral chimera, Ad5H3-HVR2-His. Ad5H3 was generated previously by substituting the hexon of Ad5 (hexon5) with the hexon from adenovirus type 3 (Ad3).
  
  
  RESULTS
  His6 was presented on the viral capsid surface and recognized by a His6 antibody. An in vitro neutralization assay with Ad5 sera indicated the ability of Ad5 chimeras to partially escape Ad5 immunity. Immunization with Ad5H3-HVR2-His generated significant humoral response to the incorporated tagged peptide, when compared to the immunizations with controls.
  
  
  CONCLUSIONS
  Based on our in vitro studies the data suggested that Ad5H3 as a novel chimeric vaccine platform yields the possibility to escape Ad5 neutralization, and the potential to generate robust humoral immunity against incorporated antigens using the "Antigen Capsid-Incorporation" strategy.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 845 19 street south, Birmingham, AL,35294, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Mert
authors.initials: M
authors.lastname: Icyuz
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 845 19 street south, Birmingham, AL,35294, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Krendelchtchikova
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 845 19 street south, Birmingham, AL,35294, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krendelchtchikov
authors.affiliation: Division of Natural Sciences and Math, Miles College, Fairfield, AL, 35064, USA.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Johnston
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 845 19 street south, Birmingham, AL,35294, USA; Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Qiana L
authors.initials: QL
authors.lastname: Matthews
keywords: Ad5 pre-existing immunity (PEI); Adenovirus type 3 (Ad3); Adenovirus type 5 (Ad5); Antigen Capsid-Incorporation strategy; Chimeric Ad5H3; Humoral immunity