A novel recombinant adeno-associated virus vaccine induces a long-term humoral immune response to human immunodeficiency virus.
Recombinant adeno-associated virus (AAV) has attracted tremendous interest as a promising vector for gene delivery. In this study we have developed an HIV-1 vaccine, using an AAV vector expressing HIV-1 env, tat, and rev genes (AAV-HIV vector). A single injection of the AAV-HIV vector induced strong production of HIV-1-specific serum IgG and fecal secretory IgA antibodies as well as MHC class I-restricted CTL activity in BALB/c mice. The titer of HIV-1-specific serum IgG remained stable for 10 months. When AAV-HIV vector was coadministered with AAV-IL2 vector, the HIV-specific cell-mediated immunity (CMI) was significantly enhanced. Boosting with AAV-HIV vector strongly enhanced the humoral response. Furthermore, the mouse antisera neutralized an HIV-1 homologous strain, and BALB/c mice immunized via the intranasal route with an AAV vector expressing the influenza virus hemagglutinin (HA) gene showed protective immunity against homologous influenza virus challenge. These results demonstrate that AAV-HIV vector immunization may provide a novel and promising HIV vaccination strategy.
Xin
K Q
KQ
Department of Bacteriology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Urabe
M
M
Yang
J
J
Nomiyama
K
K
Mizukami
H
H
Hamajima
K
K
Nomiyama
H
H
Saito
T
T
Imai
M
M
Monahan
J
J
Okuda
K
K
Ozawa
K
K
Okuda
K
K
D016915:AIDS Vaccines / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D000229:Dependovirus / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015694:Gene Products, rev / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology; D015752:Genes, env / Q000235:genetics; D015756:Genes, tat / Q000235:genetics; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D016207:Cytokines; D015694:Gene Products, rev; D015696:Gene Products, tat; D015483:HIV Antibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007106:Immune Sera; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma