Intranasal administration of HIV-DNA vaccine formulated with a polymer, carboxymethylcellulose, augments mucosal antibody production and cell-mediated immune response.
We previously reported that intramuscular (i.m.) immunization of DNA vaccine encoding human immunodeficiency virus type 1 (HIV-1)IIIB env and rev genes alone or in combination with appropriate adjuvant induces substantial and enhanced immune response against HIV-1. In the present study, we examined whether a polymer, low-viscosity carboxymethylcellulose sodium salt (CMCS-L), has an adjuvant effect on immune response induced by DNA vaccination. BALB/c mice were immunized with HIV-DNA vaccine formulated with CMCS-L via the intranasal (i.n.) and i.m. routes. The combination with the polymer elicited higher levels of antigen-specific serum IgG and fecal IgA antibodies than DNA vaccine alone. For cell-mediated immunity, HIV-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were measured by the footpad-swelling test and the 51Cr-release assay, respectively. Both were enhanced by the combination with CMCS-L via i.n. and i.m. inoculation. Cytokine analysis in culture media of bulk splenocytes harvested from immunized animals showed higher levels of IL-4 production in i.n. -immunized mice compared with i.m.-immunized mice. Nevertheless, the increased IFN-gamma production resulting from the combination with CMCS-L was observed only in i.n.-immunized mice. These data indicate that i.n. immunization of HIV-DNA vaccine formulated with CMCS-L enhances HIV-specific mucosal antibody (Ab) and systemic Ab and cell-mediated immune response.
Department of Bacteriology, Yokohama City University School of Medicine, Yokohama, 236, Japan.
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Hamajima
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Sasaki
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Fukushima
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Kaneko
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Xin
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Kudoh
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Okuda
D016915:AIDS Vaccines / Q000276:immunology* / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000097:blood; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D006678:HIV / Q000235:genetics* / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000187:drug effects*; D007074:Immunoglobulin G / Q000145:classification; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017186:Titrimetry; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000906:Antibodies; D007074:Immunoglobulin G; D011108:Polymers; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D002266:Carboxymethylcellulose Sodium