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Journal of Virology, June 2009, p. 5567-5573, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00405-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of Preexisting Immunity on an Adenovirus Vaccine Vector: In Vitro Neutralization Assays Fail To Predict Inhibition by Antiviral Antibody In Vivo{triangledown}

Susan L. Pichla-Gollon,1* Shih-Wen Lin,2,3 Scott E. Hensley,2,3 Marcio O. Lasaro,2 Larissa Herkenhoff-Haut,2 Mark Drinker,1 Nia Tatsis,2 Guang-Ping Gao,5 James M. Wilson,5 Hildegund C. J. Ertl,2 and Jeffrey M. Bergelson1,4

Division of Infectious Diseases, the Children's Hospital of Philadelphia,1 Wistar Institute,2 Program in Biomedical Graduate Studies,3 Departments of Pediatrics,4 Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania5

Received 24 February 2009/ Accepted 5 March 2009

A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8+ T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8+ T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.

* Corresponding author. Present address: GlaxoSmithKline, 2301 Renaissance Blvd., King of Prussia, PA 19406. Phone: (610) 787-3924. Fax: (610) 787-7056. E-mail: susan.l.gollon{at}gsk.com

{triangledown} Published ahead of print on 11 March 2009.

Journal of Virology, June 2009, p. 5567-5573, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00405-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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