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Journal of Virology, December 2004, p. 13207-13215, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13207-13215.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Novel Replication-Incompetent Vector Derived from Adenovirus Type 11 (Ad11) for Vaccination and Gene Therapy: Low Seroprevalence and Non-Cross-Reactivity with Ad5

Lennart Holterman,1 Ronald Vogels,1 Remko van der Vlugt,1 Martijn Sieuwerts,1 Jos Grimbergen,2 Jorn Kaspers,1 Eric Geelen,1 Esmeralda van der Helm,1 Angelique Lemckert,1 Gert Gillissen,1 Sandra Verhaagh,1 Jerome Custers,1 David Zuijdgeest,1 Ben Berkhout,3 Margreet Bakker,3 Paul Quax,2,4 Jaap Goudsmit,1 and Menzo Havenga1*

Crucell Holland BV,1 Gaubius Laboratory, TNO-PG,2 Department of Surgery, Leiden University Medical Center, Leiden,4 Department of Human Retrovirology, Academic Medical Center, Amsterdam, The Netherlands3

Received 1 June 2004/ Accepted 26 June 2004

A novel plasmid-based adenovirus vector system that enables manufacturing of replication-incompetent ({Delta}E1) adenovirus type 11 (Ad11)-based vectors is described. Ad11 vectors are produced on PER.C6/55K cells yielding high-titer vector batches after purification. Ad11 seroprevalence proves to be significantly lower than that of Ad5, and neutralizing antibody titers against Ad11 are low. Ad11 seroprevalence among human immunodeficiency virus-positive (HIV+) individuals is as low as that among HIV– individuals, independent of the level of immune suppression. The low level of coinciding seroprevalence between Ad11 and Ad35 in addition to a lack of correlation between high neutralizing antibody titers towards either adenovirus strongly suggest that the limited humoral cross-reactive immunity between these two highly related B viruses appears not to preclude the use of both vectors in the same individual. Ad11 transduces primary cells including smooth muscle cells, synoviocytes, and dendritic cells and cardiovascular tissues with higher efficiency than Ad5. Ad11 and Ad35 appear to have a similar tropism as judged by green fluorescent protein expression levels determined by using a panel of cancer cell lines. In addition, Ad5 preimmunization did not significantly affect Ad11-mediated transduction in C57BL/6 mice. We therefore conclude that the Ad11-based vector represents a novel and useful candidate gene transfer vehicle for vaccination and gene therapy.

* Corresponding author. Mailing address: P.O. Box 2048, 2301CA Leiden, The Netherlands. Phone: 31 (0)71-5248736. Fax: 31 (0)71-5248902. E-mail: m.havenga{at}crucell.com.

Journal of Virology, December 2004, p. 13207-13215, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13207-13215.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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