Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of plasmid DNA expressing CCR7 ligands.
The CCR7 ligands, secondary lymphoid tissue chemokine (SLC) and Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC), were recently recognized as key molecules in establishing functional microenvironments for the initiation of immune responses in secondary lymphoid tissue. Here, we investigated the effect of CCR7 ligands-DNA administration on systemic and mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV). Systemic co-transfer of both CCR7 ligands enhanced serum gB-specific IgG Ab but failed to elicit enhancement of distal mucosal IgA responses. In contrast, mucosal co-transfer provided significant increases of distal mucosal IgA responses. CCR7 ligands also enhanced T cell-mediated immunity as measured by CD4+ T helper cell proliferation and CD8+ T cell-mediated CTL activity. Of particular interest, is the observation that SLC significantly increased the production of Th1-type cytokines (IL-2 and IFN-gamma) (P<0.05), whereas ELC increased the production of both Th1-type and Th2-type (IL-4) cytokines (P<0.05). Moreover, co-vaccination of CCR7 ligands increased the number of dendritic cells in secondary lymphoid tissue. These data indicate that CCR7 ligands may prove to be useful adjuvants for genetic vaccination against intracellular infection as well as cancer.
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Department of Microbiology, M409 Walters Life Sciences Building, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996-0845, USA.
Lee
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Kumaraguru
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Rouse
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BT
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003587:Cytomegalovirus / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004333:Drug Administration Routes; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005813:Genes, Synthetic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D011401:Promoter Regions, Genetic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000187:drug effects*; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D007507:Therapeutic Irrigation; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D004274:DNA, Recombinant; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus