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Journal of Virology, September 2006, p. 9134-9143, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00050-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Baculovirus-Derived Human Immunodeficiency Virus Type 1 Virus-Like Particles Activate Dendritic Cells and Induce Ex Vivo T-Cell Responses

L. Buonaguro,1,2 M. L. Tornesello,1 M. Tagliamonte,1 R. C. Gallo,2 L. X. Wang,2 R. Kamin-Lewis,2,3 S. Abdelwahab,2 G. K. Lewis,2,3 and F. M. Buonaguro1*

Laboratory of Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Istituto Nazionale Tumori "Fond. G. Pascale," Naples, Italy,1 Institute of Human Virology, University of Maryland Biotechnology Institute,2 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland3

Received 9 January 2006/ Accepted 26 June 2006

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55gag virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLPAs). The HIV-VLPAs show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4+ T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLPAs in vivo.

* Corresponding author. Mailing address: Lab. Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Istituto Nazionale Tumori "Fond. G. Pascale," Via Mariano Semmola, 1, 80131 Naples, Italy. Phone: 39-081-5903.830. Fax: 39-081-5451276. E-mail: irccsvir{at}unina.it.

Journal of Virology, September 2006, p. 9134-9143, Vol. 80, No. 18
0022-538X/06/$08.00+0     doi:10.1128/JVI.00050-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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