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Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization.
Open accessAbstract
We compared the antigen-specific antibody isotypes and lymphokine secretion by CD4+ T cells in BALB/c mice immunized intradermally with either Escherichia coli beta-galactosidase (beta-gal) or plasmid DNA (pDNA) encoding beta-gal in a cytomegalovirus-based expression vector (pCMV-LacZ). pCMV-LacZ induced mainly IgG2a, whereas beta-gal in saline or alum induced IgG1 and IgE beta-gal-specific antibodies. In addition, splenic CD4+ T helper (Th) cells isolated from pDNA-immunized mice secreted interferon-gamma but not interleukin (IL)-4 and IL-5, whereas Th cells from beta-gal-injected mice secreted IL-4 and IL-5 but not interferon-gamma after in vitro stimulation with antigen. Together these data demonstrate that pDNA immunization induced a T helper type 1 (Th1) response, whereas protein immunization induced a T helper type 2 (Th2) response to the same antigen. Interestingly, priming of mice with pCMV-LacZ prevented IgE antibody formation to a subsequent i.p. beta-gal in alum injection. This effect was antigen-specific, because priming with pCMV-LacZ did not inhibit IgE anti-ovalbumin antibody formation. Most importantly, intradermal immunization with pCMV-LacZ (but not pCMV-OVA) of beta-gal in alum-primed mice caused a 66-75% reduction of the IgE anti-beta-gal titer in 6 weeks. Also, pCMV-LacZ induced specific IgG2a antibody titers and interferon-gamma secretion by Th cells in the beta-gal in alum-primed mice. The data demonstrate that gene immunization induces a Th1 response that dominates over an ongoing protein-induced Th2 response in an antigen-specific manner. This suggests that immunization with pDNA encoding for allergens may provide a novel type of immunotherapy for allergic diseases.
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Cites
Direct Gene Transfer into Mouse Muscle in Vivo
Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., & Felgner, P. L. (1990) · Science · doi:10.1126/science.1690918 · Cited by 4,173
Cited by
Allergic Rhinitis and Its Impact on Asthma
Bousquet, J., van Cauwenberge, P., & Khaltaev, N. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.118891 · Cited by 3,588
mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474
DNA Vaccines: Immunology, Application, and Optimization
Gurunathan, S., Klinman, D. M., & Seder, R. A. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.927 · Cited by 1,207
Roy, K., Mao, H.-Q., Huang, S. K., & Leong, K. W. (1999) · Nature Medicine · doi:10.1038/7385 · Cited by 1,106
Donnelly, J. J., Ulmer, J. B., Shiver, J. W., & Liu, M. A. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.617 · Cited by 987
Metadata
- Authors
- Raz, E., Tighe, H., Sato, Y., Corr, M., Dudler, J. A., Roman, M., Swain, S. L., Spiegelberg, H. L., & Carson, D. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-05-14
- Volume
- 93
- Issue
- 10
- Pages
- 5141-5145
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2084129498
- Cited by
- 515
- References
- 1
- FWCI
- 22.02
- Type
- journal article
- Language
- en
- Open access
- green
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- Raz, E., Tighe, H., Sato, Y., Corr, M., Dudler, J. A., Roman, M., Swain, S. L., Spiegelberg, H. L., & Carson, D. A. (1996). Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.10.5141
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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