Modulation of the immune response to DNA vaccine by co-delivery of costimulatory molecules.
We have investigated methods for modulating immune responses, against herpes simplex virus (HSV), generated from DNA vaccination by co-delivery of genes encoding costimulatory molecules. A strong delayed-type hypersensitivity (DTH) reaction was induced in mice co-injected via the intradermal (i.d.) route with a eukaryotic expression plasmid encoding the CD80 molecule (pCD80) and a plasmid encoding the glycoprotein D of the HSV-2 (pgD). Furthermore, when spleen cells from these mice were cultured in the presence of inactivated HSV, a significant increase in the expression of interleukin-2 receptor (IL-2R) was observed in the CD4 subset compared with mice immunized only with pgD. Analysis of cytokine synthesis at the single-cell level indicated that CD80 genes induce a significant increase in the number of interferon-gamma (IFN-gamma)-, IL-2- and IL-4-secreting cells in the spleen. On the other hand, co-administration of the CD80 gene via the intramuscular (i.m.) route did not induce an increase in the cell-mediated immune response. When a plasmid carrying the CD86 gene (pCD86) was co-injected via the i.m. route with the pgD plasmid, a small decrease in the number of IFN-gamma-secreting cells was observed. This down-regulation of the immune response was also observed when eukaryotic expression cassettes for CD80 and for CD86 were co-administered with the pgD plasmid via the i.d. route. However, co-injection of pCD86 via the i.m. route produced a small increase in the number of IL-4-secreting cells. When immunized mice were challenged intravaginally with 100 plaque-forming units of virus, only co-injection of the CD80 gene by the i.d. route provoked an adjuvant effect compared with mice immunized with pgD alone. A reduction in the titres of HSV in vaginal washings was observed together with a decrease in the lesion score.
Fló
J
J
Faculty of the Exact and Natural Sciences, University of Buenos Aires, Argentina.
Tisminetzky
S
S
Baralle
F
F
D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D018929:Cell Culture Techniques; D005260:Female; D006558:Herpes Genitalis / Q000517:prevention & control; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040570:glycoprotein D-herpes simplex virus type 2