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Journal of Virology, November 2005, p. 14161-14168, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14161-14168.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Immunogenicity of Recombinant Fiber-Chimeric Adenovirus Serotype 35 Vector-Based Vaccines in Mice and Rhesus Monkeys

Anjali Nanda,1 Diana M. Lynch,1 Jaap Goudsmit,2 Angelique A. C. Lemckert,2 Bonnie A. Ewald,1 Shawn M. Sumida,1 Diana M. Truitt,1 Peter Abbink,1 Michael G. Kishko,1 Darci A. Gorgone,1 Michelle A. Lifton,1 Ling Shen,1 Angela Carville,3 Keith G. Mansfield,3 Menzo J. E. Havenga,2 and Dan H. Barouch1*

Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215,1 Crucell Holland B.V., P.O. Box 2048, 2301 CA, Leiden, The Netherlands,2 New England Primate Research Center, Southborough, Massachusetts 017723

Received 24 June 2005/ Accepted 30 August 2005

Preexisting immunity to adenovirus serotype 5 (Ad5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. A potential solution to this problem is to utilize rAd vectors derived from rare Ad serotypes, such as Ad35. However, rAd35 vectors have appeared less immunogenic than rAd5 vectors in preclinical studies to date. In this study, we explore the hypothesis that the differences in immunogenicity between rAd5 and rAd35 vectors may be due in part to differences between the fiber proteins of these viruses. We constructed capsid chimeric rAd35 vectors containing the Ad5 fiber knob (rAd35k5) and compared the immunogenicities of rAd5, rAd35k5, and rAd35 vectors expressing simian immunodeficiency virus Gag and HIV-1 Env in mice and rhesus monkeys. In vitro studies demonstrated that rAd35k5 vectors utilized the Ad5 receptor CAR rather than the Ad35 receptor CD46. In vivo studies showed that rAd35k5 vectors were more immunogenic than rAd35 vectors in both mice and rhesus monkeys. These data suggest that the Ad5 fiber knob contributes substantially to the immunogenicity of rAd vectors. Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes.

* Corresponding author. Mailing address: Research East Room 113, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone: (617) 667-4434. Fax: (617) 667-8210. E-mail: dbarouch{at}bidmc.harvard.edu.

Journal of Virology, November 2005, p. 14161-14168, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14161-14168.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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