Contribution of IRF-3 mediated IFNβ production to DNA vaccine dependent cellular immune responses

Hidekazu Shirota; Lev Petrenko; Toshio Hattori; Dennis M. Klinman

doi:10.1016/j.vaccine.2009.01.134

Contribution of IRF-3 mediated IFNβ production to DNA vaccine dependent cellular immune responses

Hidekazu Shirota, Lev Petrenko, Toshio Hattori, Dennis M. Klinman

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNβ encoding plasmid. These findings suggest that the IRF-3/IFNβ pathways are key to the induction of cellular immunity following DNA vaccination.

Original language	English
Pages (from-to)	2144-2149
Number of pages	6
Journal	Vaccine
Volume	27
Issue number	15
DOIs	https://doi.org/10.1016/j.vaccine.2009.01.134
Publication status	Published - 2009 Mar 26

Keywords

DNA vaccine
IRF-3
Type1 IFNs

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.vaccine.2009.01.134

Cite this

@article{99e6e313803943dea354f889ae6435d2,

title = "Contribution of IRF-3 mediated IFNβ production to DNA vaccine dependent cellular immune responses",

abstract = "The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNβ encoding plasmid. These findings suggest that the IRF-3/IFNβ pathways are key to the induction of cellular immunity following DNA vaccination.",

keywords = "DNA vaccine, IRF-3, Type1 IFNs",

author = "Hidekazu Shirota and Lev Petrenko and Toshio Hattori and Klinman, {Dennis M.}",

note = "Funding Information: The authors thank Dr. Tadatsugu Taniguchi for kindly providing IRF-3 KO mice. This project was supported by funding from the intramural research program of the National Cancer Institute and contract #261200800001 E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsment by the U.S. Government",

year = "2009",

month = mar,

day = "26",

doi = "10.1016/j.vaccine.2009.01.134",

language = "English",

volume = "27",

pages = "2144--2149",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "15",

}

TY - JOUR

T1 - Contribution of IRF-3 mediated IFNβ production to DNA vaccine dependent cellular immune responses

AU - Shirota, Hidekazu

AU - Petrenko, Lev

AU - Hattori, Toshio

AU - Klinman, Dennis M.

N1 - Funding Information: The authors thank Dr. Tadatsugu Taniguchi for kindly providing IRF-3 KO mice. This project was supported by funding from the intramural research program of the National Cancer Institute and contract #261200800001 E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsment by the U.S. Government

PY - 2009/3/26

Y1 - 2009/3/26

N2 - The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNβ encoding plasmid. These findings suggest that the IRF-3/IFNβ pathways are key to the induction of cellular immunity following DNA vaccination.

AB - The mechanism(s) by which DNA vaccines activate Ag-specific cellular immune responses is incompletely understood. Current findings indicate that IRF-3 plays an important role in this process. The IRF-3 dependent signaling pathway is triggered by the presence of intracytoplasmic DNA, and culminates in the production of type I IFNs. DNA vaccination of IRF-3 KO mice elicits a strong Ag-specific humoral response, yet CD4 and CD8 T cell responses (including the production of Th1, Th2 and Th17 cytokines) are severely impaired. Although expression of the immunogenic protein encoded by the DNA vaccine was similar in IRF-3 KO vs wild type mice, antigen presentation was severely impaired in the KO animals. This defect was remedied by the co-delivery of an IFNβ encoding plasmid. These findings suggest that the IRF-3/IFNβ pathways are key to the induction of cellular immunity following DNA vaccination.

KW - DNA vaccine

KW - IRF-3

KW - Type1 IFNs

UR - http://www.scopus.com/inward/record.url?scp=61549091187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61549091187&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2009.01.134

DO - 10.1016/j.vaccine.2009.01.134

M3 - Article

C2 - 19356618

AN - SCOPUS:61549091187

SN - 0264-410X

VL - 27

SP - 2144

EP - 2149

JO - Vaccine

JF - Vaccine

IS - 15

ER -

Contribution of IRF-3 mediated IFNβ production to DNA vaccine dependent cellular immune responses

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this