Type I IFN Signaling on Both B and CD4 T Cells Is Required for Protective Antibody Response to Adenovirus

Recombinant adenoviruses have been used as vehicles for gene therapy as well as vaccination against infectious diseases and cancer. Efficient activation of host B cell response to adenoviral vectors that leads to the generation of protective, neutralizing Ab, represents a major barrier for gene ther...

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Bibliographic Details
Published in:Journal of Immunology 2007-03, Vol.178 (6), p.3505-3510
Main Authors: Zhu, Jiangao, Huang, Xiaopei, Yang, Yiping
Format: Article
Language:English
Subjects:
Adenoviridae - immunology
Adenovirus
Animals
Antibodies, Viral - immunology
Antibody Formation
Cancer Vaccines - immunology
CD4-Positive T-Lymphocytes - immunology
Genetic Therapy - methods
Genetic Vectors - immunology
Germinal Center - immunology
Immunoglobulin Class Switching - immunology
Immunoglobulin M - immunology
Interferon-gamma - deficiency
Interferon-gamma - immunology
Lymphocyte Activation
Mice
Mice, Knockout
Neoplasms - immunology
Neoplasms - therapy
Plasma Cells - immunology
Signal Transduction - immunology
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Summary:Recombinant adenoviruses have been used as vehicles for gene therapy as well as vaccination against infectious diseases and cancer. Efficient activation of host B cell response to adenoviral vectors that leads to the generation of protective, neutralizing Ab, represents a major barrier for gene therapy, but an attractive feature for vaccine development. What regulate(s) potent B cell response to adenoviral vectors remains incompletely defined. In this study, we showed that type I IFNs induced upon adenoviral infection are critical for multiple stages of adaptive B cell response to adenovirus including early B cell activation, germinal center formation, Ig isotype switching as well as plasma cell differentiation. We further demonstrated that although type I IFN signaling on dendritic cells was important for the production of virus-specific IgM, the generation of protective neutralizing Ab critically depended on type I IFN signaling on both CD4 T and B cells. The results may suggest potential strategies for improving adenovirus-mediated gene therapy in vivo and/or the design of effective vaccines for cancer and infectious diseases.
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.178.6.3505