HIV mucosal vaccine: nasal immunization with gp160-encapsulated hemagglutinating virus of Japan-liposome induces antigen-specific CTLs and neutralizing antibody responses.
Nasal immunization of normal mice with HIVgp160-encapsulated hemagglutinating virus of Japan (HVJ)-liposome induced high titers of gp160-specific neutralizing IgG in serum and IgA in nasal wash, saliva, fecal extract, and vaginal wash, along with both Th1- and Th2-type responses. HIVgp160-specific IgG- and IgA-producing cells were also detected in mononuclear cells isolated from spleen, nasal cavity, salivary gland, intestinal lamina propria, and vaginal tissue of nasally immunized mice. In addition, CD8(+) CTLs were induced in mice nasally immunized with gp160-HVJ-liposome. These findings suggest that two layers of effective HIV-specific humoral and cellular immunity, in mucosal and systemic sites, were induced by this nasal vaccine. In immunodeficient mice, nasal immunization with gp160-HVJ-liposome induced Ag-specific immune responses for the systemic and mucosal compartments of both Th1 (IFN-gamma(-/-)) and Th2 (IL-4(-/-)). In vitro Ag-specific serum IgG Ab and vaginal wash samples possessing IgA and IgG Abs that had been induced by nasal immunization with gp160-HVJ-liposome were able to neutralize a clinically isolated strain of HIV-MN strain isolated from Japanese hemophiliac patients. Taken together, these results suggest that, for the prevention and control of AIDS, nasally administered gp160-HVJ-liposome is a powerful immunization tool that induces necessary Ag-specific immune responses at different stages of HIV infection.
Sakaue
Gaku
G
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Hiroi
Takachika
T
Nakagawa
Yoko
Y
Someya
Kenji
K
Iwatani
Kohich
K
Sawa
Yoshiki
Y
Takahashi
Hidemi
H
Honda
Mitsuo
M
Kunisawa
Jun
J
Kiyono
Hiroshi
H
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000276:immunology; D000921:Antibody-Producing Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D009500:Neutralization Tests; D029082:Sendai virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008081:Liposomes