Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

MIchael G. Agadjanyan (Creator)

Davit Babikyan (Creator)

David H. Cribbs (Creator)

Anahit Ghochikyan (Creator)

Elizabeth Head (Creator)

Nina Movesesyan (Creator)

Irina Petrushina (Creator)

Ted M. Ross (Creator)

Nadya Sadzikava (Creator)

Wenqiang Tian (Creator)

Vitaly Vasilevko (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Active immunization with fibrillar beta-amyloid peptide (AB42) as well as passive transfer of anti-AB antibodies significantly reduces AB plaque deposition neuritic dystrophy and astrogliosis in the brain of mutant amyloid precursor protein (APP)-transgenic mice. Although the mechanism(s) of clearance of AB from the brain following active or passive immunization remains to be determined it is clear that anti-AB antibodies are critical for clearance. DNA immunization provides an attractive alternative to direct peptide and adjuvant approaches for inducing a humoral response to AB. We constructed a DNA minigene with AB fused to mouse interleukin-4 (pAB42-IL-4) as a molecular adjuvant to generate anti-AB antibodies and enhance the Th2-type of immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti-AB antibodies. Fine epitope analysis with overlapping peptides of the AB42 sequence identified the 1- 15 region as a dominant B cell epitope. The DNA minigeneinduced anti-AB antibodies bound to AB plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy. Originally published European Journal of Immunology Vol. 33 No. 12 Dec 2003

Additional Information

Publication

Other

European Journal of Immunology. 33:12(December 2003) p. 3232-3241.

Language: English

Date: 2011

Keywords

DNA immunization, antibodies, epitopes, Mice, antigens

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