1. ¹Department of Pharmacology and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland,USA
2. ²Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
3. ³Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA

Correspondence: Kam W. Leong, Department of Biomedical Engineering, Box 90281, Durham, North Carolina 27708, USA. E-mail: kam.leong@duke.edu

Received 13 April 2006; Accepted 25 January 2007; Published online 13 March 2007.

Abstract

Transfection of DNA vaccines with chemokines may recruit dendritic cells (DCs) locally to capture the antigenic genes and their gene products to generate enhanced CD8⁺ cytotoxic T lymphocytes (CTLs). In this study, we investigated the effects of macrophage inflammatory protein (MIP)-1, MIP-3, and MIP-3 on human immunodeficiency virus (HIV) Gag DNA vaccination. The chemokine plasmids markedly enhanced the local infiltration of inflammatory cells and increased the presence of CD11c⁺ B7.2⁺-activated DCs. MIP-1 and MIP-3 were potent adjuvants in augmenting CTLs and afforded strong protection to immunized animals against challenge with vaccinia virus expressing Gag (vv-Gag). However, decreased humoral response was observed. MIP-3 plasmid did not dramatically alter immunity. The chemokine inoculation time with respect to DNA vaccine priming was also investigated. The injection of pMIP-3 three days before Gag plasmid (pGag) vaccination markedly increased specific CTLs compared with simultaneous injection and led to higher protection against vv-Gag. Immunity was also shifted toward a T-helper type-1 (Th1) response. In contrast, inoculation with pMIP-3 three days after pGag vaccination shifted immunity toward a Th2 response. Our data suggest that administration of a chemokine with DNA vaccines offers a valuable strategy to modulate the efficacy and polarization of specific immunity and that chemokine–antigen timing is critical in determining overall biological effects.