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Journal of Virology, March 2004, p. 2666-2673, Vol. 78, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.6.2666-2673.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Neutralizing Antibodies and CD8+ T Lymphocytes both Contribute to Immunity to Adenovirus Serotype 5 Vaccine Vectors

Shawn M. Sumida,1 Diana M. Truitt,1 Michael G. Kishko,1 Janelle C. Arthur,1 Shawn S. Jackson,1 Darci A. Gorgone,1 Michelle A. Lifton,1 Wouter Koudstaal,2 Maria G. Pau,2 Stefan Kostense,2 Menzo J. E. Havenga,2 Jaap Goudsmit,2 Norman L. Letvin,1 and Dan H. Barouch1*

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Crucell Holland, Leiden, The Netherlands2

Received 1 October 2003/ Accepted 17 November 2003

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. Ad5-specific neutralizing antibodies (NAbs) are thought to contribute substantially to anti-Ad5 immunity, but the potential importance of Ad5-specific T lymphocytes in this setting has not been fully characterized. Here we assess the relative contributions of Ad5-specific humoral and cellular immune responses in blunting the immunogenicity of a rAd5-Env vaccine in mice. Adoptive transfer of Ad5-specific NAbs resulted in a dramatic abrogation of Env-specific immune responses following immunization with rAd5-Env. Interestingly, adoptive transfer of Ad5-specific CD8+ T lymphocytes also resulted in a significant and durable suppression of rAd5-Env immunogenicity. These data demonstrate that NAbs and CD8+ T lymphocytes both contribute to immunity to Ad5. Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses.

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

Journal of Virology, March 2004, p. 2666-2673, Vol. 78, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.6.2666-2673.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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