JVI Accepts, published online ahead of print on 19 March 2008

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J. Virol. doi:10.1128/JVI.02564-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of HIV-1 DNA Vaccine Immunogenicity by In Vivo Electroporation

Jinyan Liu, Rune Kjeken, Iacob Mathiesen, and Dan H. Barouch^*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Inovio Biomedical, San Diego, CA 92121

^* To whom correspondence should be addressed. Email: dbarouch{at}bidmc.harvard.edu.

In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to an HIV-1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8+ T lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold increased numbers of macrophages and 77-fold increased numbers of dendritic cells as well as 2- to 6-fold increased numbers of B and T lymphocytes as compared with infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells including APCs to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited antigen-presenting cells (APCs) to the injection site, however, did not result in synergy.

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