Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device

The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 respo...

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Main Authors: Susanne Johansson, Monica Ek, Britta Wahren, Richard Stout, Margaret A. Liu, Kristian Hallermalm
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2007.138
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author Susanne Johansson
Monica Ek
Britta Wahren
Richard Stout
Margaret A. Liu
Kristian Hallermalm
author_facet Susanne Johansson
Monica Ek
Britta Wahren
Richard Stout
Margaret A. Liu
Kristian Hallermalm
author_sort Susanne Johansson
collection DOAJ
description The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen) affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector). CEA was expressed either in a membrane-bound form (wild-type CEA) or in two truncated forms (CEA6 and CEA66) with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.
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spelling doaj-art-1460fc7ea8d64217a941d4e00af2884b2025-08-20T03:54:29ZengWileyThe Scientific World Journal1537-744X2007-01-01798799910.1100/tsw.2007.138Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection DeviceSusanne Johansson0Monica Ek1Britta Wahren2Richard Stout3Margaret A. Liu4Kristian Hallermalm5Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenCenter for Molecular Medicine, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenBioject Medical Technologies Inc., Tualatin, OR, USADepartment of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenThe route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen) affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector). CEA was expressed either in a membrane-bound form (wild-type CEA) or in two truncated forms (CEA6 and CEA66) with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.http://dx.doi.org/10.1100/tsw.2007.138
spellingShingle Susanne Johansson
Monica Ek
Britta Wahren
Richard Stout
Margaret A. Liu
Kristian Hallermalm
Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
The Scientific World Journal
title Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
title_full Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
title_fullStr Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
title_full_unstemmed Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
title_short Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device
title_sort intracellular targeting of cea results in th1 type antibody responses following intradermal genetic vaccination by a needle free jet injection device
url http://dx.doi.org/10.1100/tsw.2007.138
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