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Journal of Virology, October 2009, p. 10596-10604, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01170-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys{triangledown}

Yue Sun,1 Robert T. Bailer,2 Srinivas S. Rao,2 John R. Mascola,2 Gary J. Nabel,2 Richard A. Koup,2 and Norman L. Letvin1,2*

Division of Viral Pathogenesis, Department of Medicine, 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 208922

Received 8 June 2009/ Accepted 29 July 2009

The administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. To explore this possibility, we evaluated T-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rAd5) prime or boost immunizations in rhesus monkeys. We also evaluated the kinetics of T-lymphocyte activation in both the systemic and the mucosal compartments after rAd5 administration in monkeys with preexisting immunity to Ad5. The rAd5 immunization induced lower-frequency Gag epitope-specific CD8+ T cells in the colonic mucosa than in the peripheral blood. There was evidence of an expansion of the simian immunodeficiency virus Gag-specific CD8+ T-cell responses, but not the Ad5 hexon-specific T-cell responses, following a homologous rAd5 boost. A striking but transient T-lymphocyte activation in both the systemic and the mucosal compartments of rhesus monkeys was observed after rAd5 immunization. These findings indicate that the administration of a vaccine vector such as Ad5 can induce a global activation of T cells.


* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Science, 330 Brookline Avenue, Boston, MA 02115. Phone: (617) 735-4400. Fax: (617) 735-4527. E-mail: nletvin{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 5 August 2009.


Journal of Virology, October 2009, p. 10596-10604, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.01170-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.