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Journal of Virology, June 2006, p. 5523-5530, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02667-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Epitopes Expressed in Different Adenovirus Capsid Proteins Induce Different Levels of Epitope-Specific Immunity

Anja Krause,1 Ju H. Joh,1 Neil R. Hackett,3 Peter W. Roelvink,4,{dagger} Joseph T. Bruder,4 Thomas J. Wickham,4,{ddagger} Imre Kovesdi,4,§ Ronald G. Crystal,1,3 and Stefan Worgall1,2*

Department of Genetic Medicine,1 Department of Pediatrics,2 Belfer Gene Therapy Core Facility, Weill Medical College of Cornell University, New York, New York,3 GenVec, Inc., Gaithersburg, Maryland4

Received 20 December 2005/ Accepted 7 March 2006

On the basis of the concept that the capsid proteins of adenovirus (Ad) gene transfer vectors can be genetically manipulated to enhance the immunogenicity of Ad-based vaccines, the present study compared the antiantigen immunogenicity of Ad vectors with a common epitope of the hemagglutinin (HA) protein of the influenza A virus incorporated into the outer Ad capsid protein hexon, penton base, fiber knob, or protein IX. Incorporation of the same epitope into the different capsid proteins provided insights into the correlation between epitope position and antiepitope immunity. Following immunization of three different strains of mice (C57BL/6, BALB/c, and CBA) with either an equal number of Ad particles (resulting in a different total HA copy number) or different Ad particle numbers (to achieve the same HA copy number), the highest primary (immunoglobulin M [IgM]) and secondary (IgG) anti-HA humoral and cellular CD4 gamma interferon and interleukin-4 responses against HA were always achieved with the Ad vector carrying the HA epitope in fiber knob. These observations suggest that the immune response against an epitope inserted into Ad capsid proteins is not necessarily dependent on the capsid protein number and imply that the choice of incorporation site in Ad capsid proteins in their use as vaccines needs to be compared in vivo.

* Corresponding author. Mailing address: Department of Genetic Medicine, Weill Medical College of Cornell University, 515 East 71st Street, S-1000, New York, NY 10021. Phone: (212) 746-2258. Fax: (212) 746-8383. E-mail: geneticmedicine{at}med.cornell.edu.

{dagger} Present address: Benitec, Inc., St. Lucia, Australia.

{ddagger} Present address: EMD Lexigen, Billerica, Mass.

§ Present address: KILA Consultants, LLC, Rockville, Md.

Journal of Virology, June 2006, p. 5523-5530, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02667-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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