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TheScientificWorldJOURNAL
Volume 7 (2007), Pages 987-999
http://dx.doi.org/10.1100/tsw.2007.138
Research Article

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

1Department of Microbiology and Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
2Swedish Institute for Infectious Disease Control, Stockholm, Sweden
3Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
4Bioject Medical Technologies Inc., Tualatin, OR, USA

Received 5 February 2007; Revised 25 April 2007; Accepted 12 May 2007

Academic Editor: Mauro Perretti

Copyright © 2007 Susanne Johansson et al.

Abstract

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.