Intranasal immunization of a DNA vaccine with IL-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing plasmids in liposomes induces strong mucosal and cell-mediated immune responses against HIV-1 antigens.
A DNA vaccine constructed with the CMV promoter conjugated to env gp160 and rev genes has been shown to induce an effective Th1-type immune response when inoculated via an intramuscular route. In the present study, we obtained high levels of both humoral and cell-mediated immune activity by intranasal administration of this DNA vaccine. The production of mucosal IgA Ab in feces and vaginal fluid was stimulated significantly by intranasal DNA administration. This route of administration resulted in a significant level of HIV-1-neutralizing Abs in feces and serum. Cytokine assays revealed that intranasal administration of this DNA vaccine induces a Th2-type immune response. Interestingly, cationic liposomes greatly enhanced these activities. Abs against HIV-1 were present for at least 10 mo. Coadministration of the DNA vaccine with IL-12- and granulocyte/macrophage-CSF-expressing plasmids induced high levels of HIV-specific CTLs and an increase in delayed type hypersensitivity when administered by the intranasal route. These results clearly demonstrate that intranasal administration of this DNA vaccine with liposomes, together with IL-12- and/or granulocyte/macrophage-CSF-expressing plasmids, induces a strong level of anti-HIV-1 immune response.
Okada
E
E
Department of Bacteriology, Yokohama City University School of Medicine, Japan.
Sasaki
S
S
Ishii
N
N
Aoki
I
I
Yasuda
T
T
Nishioka
K
K
Fukushima
J
J
Miyazaki
J
J
Wahren
B
B
Okuda
K
K
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D002459:Cell Fusion / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004337:Drug Carriers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D016207:Cytokines; D004337:Drug Carriers; D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008081:Liposomes; D019444:Vaccines, DNA; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor