Immune responses against replication-deficient adenovirus inhibit ovalbumin-specific allergic reactions in mice.
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 BALF 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.
Suzuki
M
M
First Department of Internal Medicine, Yokohama City University School of Medicine, Kanazawa, Yokohama, Japan. motosuzuki@email.msn.com
Suzuki
S
S
Yamamoto
N
N
Komatsu
S
S
Inoue
S
S
Hashiba
T
T
Nishikawa
M
M
Ishigatsubo
Y
Y
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002645:Chickens; D004804:Eosinophils / Q000473:pathology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D018418:Th2 Cells / Q000276:immunology
D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin