title: Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the induction of HIV Gag-specific immune response with DNA vaccines.
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 alpha, MIP-3 alpha, and MIP-3beta 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 alpha and MIP-3 alpha 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-3beta plasmid did not dramatically alter immunity. The chemokine inoculation time with respect to DNA vaccine priming was also investigated. The injection of pMIP-3 alpha 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 alpha 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.
authors.affiliation: Department of Pharmacology and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ruijiang
authors.initials: R
authors.lastname: Song
authors.forename: Shuqin
authors.initials: S
authors.lastname: Liu
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
mesh_terms: D000818:Animals; D002460:Cell Line; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D006678:HIV / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D054407:Chemokine CCL4; D015683:Gene Products, gag; D019402:Macrophage Inflammatory Proteins; D020033:Protein Isoforms; D019444:Vaccines, DNA