A novel immunization method to induce cytotoxic T-lymphocyte responses (CTL) against plasmid-encoded herpes simplex virus type-1 glycoprotein D.
DNA molecules complexed with an asialoglycoprotein-polycation conjugate, consisting of asialoorosomucoid (ASOR) coupled to poly-L-lysine, can enter hepatocytes which bear receptors for ASOR. We used this receptor-mediated DNA delivery system to deliver plasmid DNA encoding glycoprotein D (gD) of herpes simplex virus type 1 to ASOR-positive cells. Maximum expression of gD protein was seen at 3 days after injection of this preparation in approximately 13% of cells from BALB/c mice [hepatocytes from mice injected intravenously (i.v.) or peritoneal exudate cells from mice injected intraperitoneally (i.p.)]. In comparison with mice injected with either the plasmid vector alone or the gD-containing plasmid uncomplexed to ASOR, mice immunized with gD-containing plasmid complexed with ASOR-poly-L-lysine induced marked antigen-specific CTL responses. BALB/c mice immunized with gD-DNA developed a T-cell-mediated CTL response against target cells expressing gD and MHC class II glycoproteins, but not against cells expressing only gD and MHC class I molecules. In C3H mice, gD-DNA induced a T-cell-mediated CTL response against target cells expressing gD and class I MHC molecules. Serum anti-gD antibody in low titers were produced in both strains of mice. DNA complexed with ASOR-poly-L-lysine induced CTL responses in mice.
Cruz
P E
PE
Department of Microbiology, Wright State University, Dayton, OH 45435, USA.
Khalil
P L
PL
Dryden
T D
TD
Chiou
H C
HC
Fink
P S
PS
Berberich
S J
SJ
Bigley
N J
NJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D011107:Polylysine / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014611:Vaccination / Q000379:methods*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000276:immunology*
D000914:Antibodies, Viral; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D015704:CD4 Antigens; D006389:Hemagglutinins, Viral; D009961:Orosomucoid; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; C017030:asialoorosomucoid; C039447:glycoprotein D, Human herpesvirus 1; D011107:Polylysine