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Journal of Virology, May 2008, p. 4844-4852, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02616-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys{triangledown}

Jinyan Liu,1 Bonnie A. Ewald,1 Diana M. Lynch,1 Matthew Denholtz,1 Peter Abbink,1 Angelique A. C. Lemckert,2 Angela Carville,3 Keith G. Mansfield,3 Menzo J. Havenga,2 Jaap Goudsmit,2 and Dan H. Barouch1*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Crucell Holland BV, 2301 CA, Leiden, The Netherlands,2 New England Primate Research Center, Southborough, Massachusetts 017723

Received 9 December 2007/ Accepted 3 March 2008

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-{gamma}+) and IFN-{gamma}+/tumor necrosis factor alpha+ (TNF-{alpha}+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-{gamma}+/TNF-{alpha}+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.

* Corresponding author. Mailing address: Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone: (617) 667-4434. Fax: (617) 667-8210. E-mail: dbarouch{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 12 March 2008.

Journal of Virology, May 2008, p. 4844-4852, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02616-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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