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Journal of Virology, May 2005, p. 6516-6522, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6516-6522.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Replication-Defective Adenovirus Serotype 5 Vectors Elicit Durable Cellular and Humoral Immune Responses in Nonhuman Primates

Sampa Santra,1 Michael S. Seaman,1 Ling Xu,2 Dan H. Barouch,1 Carol I. Lord,1 Michelle A. Lifton,1 Darci A. Gorgone,1 Kristin R. Beaudry,1 Krisha Svehla,2 Brent Welcher,2 Bimal K. Chakrabarti,2 Yue Huang,2 Zhi-Yong Yang,2 John R. Mascola,2 Gary J. Nabel,2 and Norman L. Letvin1,2*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-30052

Received 22 November 2004/ Accepted 5 January 2005

The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P. O. Box 15732, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

Journal of Virology, May 2005, p. 6516-6522, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6516-6522.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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