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Journal of Virology, March 2002, p. 2667-2675, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2667-2675.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Novel, Chimpanzee Serotype 68-Based Adenoviral Vaccine Carrier for Induction of Antibodies to a Transgene Product

Zhiquan Xiang,1 Guangping Gao,2 Arturo Reyes-Sandoval,1,3 Christopher J. Cohen,4 Yan Li,1 Jeffrey M. Bergelson,4 James M. Wilson,2 and Hildegund C. J. Ertl1*

The Wistar Institute,1 Institute for Human Gene Therapy of the University of Pennsylvania,2 Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104,4 Posgrado en Biomedicina Molecular, Centro de Investigacion en Ciencia Aplicada y Tecnologia Avanzada del I.P.N. (CICATA-IPN), Mexico City, Mexico3

Received 19 September 2001/ Accepted 26 November 2001

An E1-deletion-containing adenoviral recombinant based on the chimpanzee serotype 68 (AdC68) was developed to express the rabies virus glycoprotein. Mice immunized with this construct (AdC68rab.gp) developed antibodies to rabies virus and remained resistant to challenge with an otherwise lethal dose of rabies virus. In naïve mice immunized intranasally, the rabies virus-specific antibody responses elicited by AdC68rab.gp were comparable with regard to both titers and isotype profiles to those induced by an adenoviral recombinant based on human serotype 5 (Adhu5) expressing the same transgene product. In contrast, subcutaneous immunization with the AdC68rab.gp vaccine resulted in markedly lower antibody responses to the rabies virus glycoprotein than the corresponding Adhu5 vaccine. Antibodies from AdC68rab.gp-immunized mice were strongly biased towards the immunoglobulin G2a isotype. The antibody response to the rabies virus glycoprotein presented by Adhu5rab.gp was severely compromised in animals preexposed to the homologous adenovirus. In contrast, the rabies virus-specific antibody response to the AdC68rab.gp vaccine was at most marginally affected by preexisting immunity to common human adenovirus serotypes, such as 2, 4, 5, 7, and 12. This novel vaccine carrier thus offers a distinct advantage over adenoviral vaccines based on common human serotypes.

* Corresponding author. Mailing address: The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-3863. Fax: (215) 898-3953. E-mail: ertl{at}wistar.upenn.edu.

Journal of Virology, March 2002, p. 2667-2675, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2667-2675.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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