Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice

被引:19
作者
Suzuki, M [1 ]
Suzuki, S [1 ]
Yamamoto, N [1 ]
Komatsu, S [1 ]
Inoue, S [1 ]
Hashiba, T [1 ]
Nishikawa, M [1 ]
Ishigatsubo, Y [1 ]
机构
[1] Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 2360004, Japan
关键词
D O I
10.1089/10430340050015446
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Replication-deficient adenovirus vector (Ad) is one of the most efficient gene transfer vehicles for human gene therapy. However, Ad is antigenic, known to evoke prominent inflammatory responses in vivo, and there are concerns that using Ad in patients with immune-mediated disorders (allergy and autoimmune diseases) may affect the status of the diseases. To evaluate this concept in a manner close to clinical scenarios, a mouse model of airway eosinophilic inflammation was developed by administering intraperitoneal injections and inhalations of chicken ovalbumin (OA), with Ad administered intranasally 5 days after the OA sensitization, The administration of Ad resulted in a significant suppression of eosinophil counts in peripheral blood as well as in the bronchoalveolar lavage fluid (BALF), and a decrease in OA-specific IgE, The decrease in the number of eosinophils in BALE was associated with a marked upregulation of interferon gamma (IFN-gamma) expression. In contrast, the Ad-specific, delayed-type hypersensitivity response and efficacy of reporter gene expression mediated by Ad were only marginally affected in animals sensitized with OA, Together, these data support the idea that Ad administration in patients with Th2-mediated immune disorders does not exacerbate the parameters of ongoing inflammations or gene transfer efficiency, and with its ability to induce prominent type 1 immune response to the antigen in vivo, Ad could potentially be used as an efficient adjuvant to control immune disorders where Th2 cell-mediated mechanisms are involved.
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页码:827 / 838
页数:12
相关论文
共 68 条
[41]   INVIVO TRANSFER OF THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE TO THE AIRWAY EPITHELIUM [J].
ROSENFELD, MA ;
YOSHIMURA, K ;
TRAPNELL, BC ;
YONEYAMA, K ;
ROSENTHAL, ER ;
DALEMANS, W ;
FUKAYAMA, M ;
BARGON, J ;
STIER, LE ;
STRATFORDPERRICAUDET, L ;
PERRICAUDET, M ;
GUGGINO, WB ;
PAVIRANI, A ;
LECOCQ, JP ;
CRYSTAL, RG .
CELL, 1992, 68 (01) :143-155
[42]   ADENOVIRUS-MEDIATED TRANSFER OF A RECOMBINANT ALPHA-L-ANTITRYPSIN GENE TO THE LUNG EPITHELIUM INVIVO [J].
ROSENFELD, MA ;
SIEGFRIED, W ;
YOSHIMURA, K ;
YONEYAMA, K ;
FUKAYAMA, M ;
STIER, LE ;
PAAKKO, PK ;
GILARDI, P ;
STRATFORDPERRICAUDET, LD ;
PERRICAUDET, M ;
JALLAT, S ;
PAVIRANI, A ;
LECOCQ, JP ;
CRYSTAL, RG .
SCIENCE, 1991, 252 (5004) :431-434
[43]   Delayed-type hypersensitivity response to high doses of adenoviral vectors [J].
Russi, TJ ;
Hirschowitz, EA ;
Crystal, RG .
HUMAN GENE THERAPY, 1997, 8 (03) :323-330
[44]   Immunostimulatory DNA sequences necessary for effective intradermal gene immunization [J].
Sato, Y ;
Roman, M ;
Tighe, H ;
Lee, D ;
Corr, M ;
Nguyen, MD ;
Silverman, GJ ;
Lotz, M ;
Carson, DA ;
Raz, E .
SCIENCE, 1996, 273 (5273) :352-354
[45]   INCREASE IN ASTHMA - A MORE TOXIC ENVIRONMENT OR A MORE SUSCEPTIBLE POPULATION [J].
SEATON, A ;
GODDEN, DJ ;
BROWN, K .
THORAX, 1994, 49 (02) :171-174
[46]   INTRAPERITONEAL IN-VIVO GENE-THERAPY TO DELIVER ALPHA-1-ANTITRYPSIN TO THE SYSTEMIC CIRCULATION [J].
SETOGUCHI, Y ;
JAFFE, HA ;
CHU, CS ;
CRYSTAL, RG .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 10 (04) :369-377
[47]   Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo [J].
Sharma, DP ;
Ramsay, AJ ;
Maguire, DJ ;
Rolph, MS ;
Ramshaw, IA .
JOURNAL OF VIROLOGY, 1996, 70 (10) :7103-7107
[48]   ADENOVIRUS-MEDIATED EXPRESSION OF THERAPEUTIC PLASMA-LEVELS OF HUMAN FACTOR-IX IN MICE [J].
SMITH, TAG ;
MEHAFFEY, MG ;
KAYDA, DB ;
SAUNDERS, JM ;
YEI, S ;
TRAPNELL, BC ;
MCCLELLAND, A ;
KALEKO, M .
NATURE GENETICS, 1993, 5 (04) :397-402
[49]   Dendritic cells genetically modified with an adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity [J].
Song, W ;
Kong, HL ;
Carpenter, H ;
Torii, H ;
Granstein, R ;
Rafii, S ;
Moore, MAS ;
Crystal, RG .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (08) :1247-1256
[50]   Cytotoxic T lymphocyte responses to proteins encoded by heterologous transgenes transferred in vivo by adenoviral vectors [J].
Song, WR ;
Kong, HL ;
Traktman, P ;
Crystal, RG .
HUMAN GENE THERAPY, 1997, 8 (10) :1207-1217