title: Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approach.
abstract: Despite the many potential advantages of Ad vectors for vaccine application, the full utility of current Ad vaccines may be limited by the host anti-vector immune response. Direct incorporation of antigens into the adenovirus capsid offers a new and exciting approach for vaccination strategies; this strategy exploits the inherent antigenicity of the Ad vector. Critical to exploiting Ad in this new context is the placement of antigenic epitopes within the major Ad capsid protein, hexon. In our current study we illustrate that we have the capability to place a range of antigenic epitopes within Ad5 capsid protein hexon hypervariable regions (HVRs) 2 or 5, thus producing viable Ad virions. Our data define the maximal incorporation size at HVR2 or HVR5 as it relates to identical antigenic epitopes. In addition, this data suggests that Ad5 HVR5 is more permissive to a range of insertions. Most importantly, repeated administration of our hexon-modified viruses resulted in a secondary anti-antigen response, whereas minimal secondary effect was present after administration of Ad5 control. Our study describes antigen placement and optimization within the context of the capsid incorporation approach of Ad vaccine employment, thereby broadening this new methodology.
authors: Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, USA. qlm@uab.edu
authors: Qiana L
authors: QL
authors: Matthews
authors: PingAr
authors: P
authors: Yang
authors: Qi
authors: Q
authors: Wu
authors: Natalya
authors: N
authors: Belousova
authors: Angel A
authors: AA
authors: Rivera
authors: Mariam A
authors: MA
authors: Stoff-Khalili
authors: Reinhard
authors: R
authors: Waehler
authors: Hui-Chen
authors: HC
authors: Hsu
authors: Zan
authors: Z
authors: Li
authors: Jing
authors: J
authors: Li
authors: John D
authors: JD
authors: Mountz
authors: Hongju
authors: H
authors: Wu
authors: David T
authors: DT
authors: Curiel
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D036022:Capsid Proteins; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C018315:hexon capsid protein, Adenovirus