Induction of dendritic cell-mediated immune responses against HIV-1 by antigen-capturing nanospheres in mice.
Prophylactic vaccines, designed to elicit potent humoral and cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens in mucosa, are the important approach to the protection of individuals against HIV-1 infection, since HIV-1 transmission is largely a result of sexual contact. In this study, a novel strategy has been developed to induce HIV-1-specific immune responses, which involves inactivated HIV-1-caputring concanavalin A (Con A)-immobilized nanospheres (HIV-NS) and their interaction with bone marrow (BM)-derived dendritic cells. HIV-NS were taken up by dendritic cells via cytoskeleton-dependent but mannose-binding site-independent phagocytosis. Serial stimulations to unprimed T-cells with HIV-1 gp120-capturing NS-pulsed dendritic cells could induce antigen-specific T-cell response. Intranasal administration of fluorescein isothiocyanate-labeled nanospheres (NS) in mice proved that the particles were taken up into pulmonary dendritic cells. Analysis of mice receiving intranasal immunizations with HIV-NS revealed that the mice efficiently induced the antibodies against HIV-1 in the genital tract and specific cytotoxic T-cells in the spleen. These results suggest that the use of HIV-1-NS may provide a novel and promising approach for the induction of humoral and cellular immune responses to HIV-1.
Kawamura
Masaki
M
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Wang
Xin
X
Uto
Tomofumi
T
Sato
Katsuaki
K
Ueno
Masamichi
M
Akagi
Takami
T
Hiraishi
Katsuya
K
Matsuyama
Takami
T
Akashi
Mitsuru
M
Baba
Masanori
M
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity; D001853:Bone Marrow; D018920:Coculture Techniques; D003208:Concanavalin A; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005836:Genitalia, Female / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D043942:Nanotubes; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D003208:Concanavalin A; D007371:Interferon-gamma; D016650:Fluorescein-5-isothiocyanate