Plasmids encoding granulocyte-macrophage colony-stimulating factor and CD154 enhance the immune response to genetic vaccines.
We examined whether plasmids encoding granulocyte-macrophage colony-stimulating factor (pGM-CSF) or CD40-ligand (pCD40L) could modify the immune response to antigen encoded by co-injected plasmid DNA. For this we used as antigen Escherichia coli beta galactosidase (beta-gal), encoded by the plasmid pLacZ. We found that intradermal co-injection of pLacZ with both pGM-CSF and pCD40L enhanced the anti-beta-gal IgG response by approximately two orders of magnitude compared to injections of pLacZ alone. Co-injection of both pGM-CSF and pCD40L with pLacZ significantly enhanced antigen-specific IgG, and in particular IgG(2a), over that of animals co-injected with pLacZ and either pGM-CSF or pCD40L. We found that co-injection of pGM-CSF and pCD40L with pLacZ enhanced the generation of beta-gal-specific cytotoxic T cells, and allowed for a significant expansion of CD8(+) T cells from splenocytes co-cultured with beta-gal expressing stimulator cells. The immunostimulatory effects induced by pGM-CSF or pCD40L required injection of these plasmids to the same site that received pLacZ. 'Priming' experiments, where the site of injection was pre-injected with either plasmid adjuvant, showed that pGM-CSF, but not pCD40L, could enhance the anti-beta-gal immune response induced by subsequently administered plasmid antigen. We conclude that plasmids encoding GM-CSF and CD154 are particularly effective genetic adjuvants when used together to enhance the humoral and cellular immune response to a plasmid-encoded antigen.
Division of Hematology/Oncology, Department of Medicine and UCSD Gene Therapy Program, University of California San Diego (UCSD) School of Medicine, La Jolla, CA 92093-0663, USA.
J A
JA
Burger
R B
RB
Mendoza
T J
TJ
Kipps
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001616:beta-Galactosidase