Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approach.

Virology Journal
Qiana L MatthewsDavid T Curiel

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 broa...Continue Reading

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Citations

Apr 25, 2013·Human Gene Therapy·Jonathan B RosenbergRonald G Crystal
Nov 21, 2012·PloS One·Justin W FlattPhoebe L Stewart
Apr 5, 2013·PloS One·Linlin GuQiana L Matthews
Jan 27, 2011·Drug Design, Development and Therapy·Lena J Gamble, Qiana L Matthews
Jan 1, 2011·Therapeutic Delivery·Anja Krause, Stefan Worgall
May 28, 2013·Vaccine·Cailin DealGary Ketner
Jun 30, 2009·Molecular BioSystems·David Papapostolou, Stefan Howorka
Apr 27, 2019·PloS One·Christopher M GentileJason M Warram
Jun 3, 2009·Expert Review of Vaccines·Erin E ThackerQiana L Matthews
Jun 13, 2015·The Open Virology Journal·Satyender HansraAlexander N Zakhartchouk
Jul 28, 2018·Biomedicines·Marija Vujadinovic, Jort Vellinga
Jun 12, 2012·Bioconjugate Chemistry·Yoon Hyeun Oum, Isaac S Carrico
Sep 14, 2010·Journal of the American Chemical Society·Partha Sarathi BanerjeeIsaac Carrico
Oct 26, 2018·Molecular Pharmaceutics·Claudia A J van WinkelDavid T Curiel

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Methods Mentioned

BETA
X-ray
PCR
ELISA
enzyme-linked immunosorbent assay
flow cytometry
electrophoresis
transfection
genetic modifications

Software Mentioned

Emboss
FlowJo

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