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Journal of Virology, March 2001, p. 2142-2153, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2142-2153.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8+ and CD4+ T-Cell Responses from Chronically Infected Individuals

Jose Engelmayer,1 Marie Larsson,1 Andrew Lee,1 Marina Lee,1 William I. Cox,2 Ralph M. Steinman,1 and Nina Bhardwaj1,*

Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York,1 and Virogenetics Corporation, Troy,2 New York

Received 31 July 2000/Accepted 29 November 2000

Recombinant canarypox virus vectors containing human immunodeficiency virus type 1 (HIV-1) sequences are promising vaccine candidates, as they replicate poorly in human cells. However, when delivered intramuscularly the vaccines have induced inconsistent and in some cases transient antigen-specific cytotoxic T-cell (CTL) responses in seronegative volunteers. An attractive way to enhance these responses would be to target canarypox virus to professional antigen-presenting cells such as dendritic cells (DCs). We studied (i) the interaction between canarypox virus and DCs and (ii) the T-cell responses induced by DCs infected with canarypox virus vectors containing HIV-1 genes. Mature and not immature DCs resisted the cytopathic effects of canarypox virus and elicited strong effector CD8+ T-cell responses from chronically infected HIV+ individuals, e.g., cytolysis, and secretion of gamma interferon (IFN-gamma ) and beta -chemokines. Furthermore, canarypox virus-infected DCs were >30-fold more efficient than monocytes and induced responses that were comparable to those induced by vaccinia virus vectors or peptides. Addition of exogenous cytokines was not necessary to elicit CD8+ effector cells, although the presence of CD4+ T cells was required for their expansion and maintenance. Most strikingly, canarypox virus-infected DCs were directly able to stimulate HIV-specific, IFN-gamma -secreting CD4 helper responses from bulk as well as purified CD4+ T cells. Therefore, these results suggest that targeting canarypox virus vectors to mature DCs could potentially elicit both anti-HIV CD8+ and CD4+ helper responses in vivo.

* Corresponding author. Mailing address: The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8332. Fax: (212) 327-8875. E-mail: bhardwn{at}rockvax.rockefeller.edu.

Journal of Virology, March 2001, p. 2142-2153, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2142-2153.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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