Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approach.
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.
Matthews
Qiana L
QL
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, Birmingham, USA. qlm@uab.edu
Yang
PingAr
P
Wu
Qi
Q
Belousova
Natalya
N
Rivera
Angel A
AA
Stoff-Khalili
Mariam A
MA
Waehler
Reinhard
R
Hsu
Hui-Chen
HC
Li
Zan
Z
Li
Jing
J
Mountz
John D
JD
Wu
Hongju
H
Curiel
David T
DT
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
D000941:Antigens; D036022:Capsid Proteins; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C018315:hexon capsid protein, Adenovirus