Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease

Research output: Contribution to journalArticle

Bao Xi Qu, Doris Lambracht-Washington, Min Fu, Todd N. Eagar, Olaf Stüve, Roger N. Rosenberg

In an effort to optimize DNA immunization-elicited antibody production responses against Aβ1-42 (Aβ42) as a therapy for Alzheimer's disease (AD), comparisons were made between three distinct plasmid systems using gene gun delivery. Plasmids encoding Aβ42 monomer and a novel Aβ42 trimeric fusion protein were evaluated in conjunction with CMV or Gal4/UAS promoter elements. It was found that vaccination Aβ42 trimer under the Gal4/UAS promoter elicited high levels of anti-Aβ42 antibody production. Serum antibody levels from Gal4/UAS-Aβ42 trimer immunized mice were found to be 16.6 ± 5.5 μg/ml compared to 6.5 ± 2.5 μg/ml with Gal4/UAS-Aβ42 monomer or even less with CMV-Aβ42 trimer. As compared to monomeric Aβ42 or Aβ42 trimer expressed under the CMV promoter, injection of the Gal4/UAS-Aβ42 trimer induced high levels of Aβ42 antigen expression in tissue suggesting a mechanism for the increase in anti-Aβ42 antibody. Antibodies were found to be primarily IgG1 suggesting a predominant Th2 response (IgG1/IgG2a ratio of 9). Serum from Aβ42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. These results demonstrate the potential therapeutic use of Gal4/UAS DNA Aβ42 trimer immunization in preventing Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)5280-5287
Number of pages8
JournalVaccine
Volume28
Issue number32
DOIs
StatePublished - Jul 1 2010

PMID: 20562015

PMCID: PMC2926979

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Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease. / Qu, Bao Xi; Lambracht-Washington, Doris; Fu, Min; Eagar, Todd N.; Stüve, Olaf; Rosenberg, Roger N.

In: Vaccine, Vol. 28, No. 32, 01.07.2010, p. 5280-5287.

Research output: Contribution to journalArticle

Harvard

Qu, BX, Lambracht-Washington, D, Fu, M, Eagar, TN, Stüve, O & Rosenberg, RN 2010, 'Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease' Vaccine, vol. 28, no. 32, pp. 5280-5287. https://doi.org/10.1016/j.vaccine.2010.05.054

APA

Qu, B. X., Lambracht-Washington, D., Fu, M., Eagar, T. N., Stüve, O., & Rosenberg, R. N. (2010). Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease. Vaccine, 28(32), 5280-5287. https://doi.org/10.1016/j.vaccine.2010.05.054

Vancouver

Qu BX, Lambracht-Washington D, Fu M, Eagar TN, Stüve O, Rosenberg RN. Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease. Vaccine. 2010 Jul 1;28(32):5280-5287. https://doi.org/10.1016/j.vaccine.2010.05.054

Author

Qu, Bao Xi ; Lambracht-Washington, Doris ; Fu, Min ; Eagar, Todd N. ; Stüve, Olaf ; Rosenberg, Roger N. / Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease. In: Vaccine. 2010 ; Vol. 28, No. 32. pp. 5280-5287.

BibTeX

@article{9b1b34573bfd4eb0bafff96ec9ffee32,
title = "Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease",
abstract = "In an effort to optimize DNA immunization-elicited antibody production responses against Aβ1-42 (Aβ42) as a therapy for Alzheimer's disease (AD), comparisons were made between three distinct plasmid systems using gene gun delivery. Plasmids encoding Aβ42 monomer and a novel Aβ42 trimeric fusion protein were evaluated in conjunction with CMV or Gal4/UAS promoter elements. It was found that vaccination Aβ42 trimer under the Gal4/UAS promoter elicited high levels of anti-Aβ42 antibody production. Serum antibody levels from Gal4/UAS-Aβ42 trimer immunized mice were found to be 16.6 ± 5.5 μg/ml compared to 6.5 ± 2.5 μg/ml with Gal4/UAS-Aβ42 monomer or even less with CMV-Aβ42 trimer. As compared to monomeric Aβ42 or Aβ42 trimer expressed under the CMV promoter, injection of the Gal4/UAS-Aβ42 trimer induced high levels of Aβ42 antigen expression in tissue suggesting a mechanism for the increase in anti-Aβ42 antibody. Antibodies were found to be primarily IgG1 suggesting a predominant Th2 response (IgG1/IgG2a ratio of 9). Serum from Aβ42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. These results demonstrate the potential therapeutic use of Gal4/UAS DNA Aβ42 trimer immunization in preventing Alzheimer's disease.",
keywords = "Alzheimer's disease, Aβ42 peptide, DNA Aβ42 immunization",
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RIS

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T1 - Analysis of three plasmid systems for use in DNA Aβ42 immunization as therapy for Alzheimer's disease

AU - Qu, Bao Xi

AU - Lambracht-Washington, Doris

AU - Fu, Min

AU - Eagar, Todd N.

AU - Stüve, Olaf

AU - Rosenberg, Roger N.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - In an effort to optimize DNA immunization-elicited antibody production responses against Aβ1-42 (Aβ42) as a therapy for Alzheimer's disease (AD), comparisons were made between three distinct plasmid systems using gene gun delivery. Plasmids encoding Aβ42 monomer and a novel Aβ42 trimeric fusion protein were evaluated in conjunction with CMV or Gal4/UAS promoter elements. It was found that vaccination Aβ42 trimer under the Gal4/UAS promoter elicited high levels of anti-Aβ42 antibody production. Serum antibody levels from Gal4/UAS-Aβ42 trimer immunized mice were found to be 16.6 ± 5.5 μg/ml compared to 6.5 ± 2.5 μg/ml with Gal4/UAS-Aβ42 monomer or even less with CMV-Aβ42 trimer. As compared to monomeric Aβ42 or Aβ42 trimer expressed under the CMV promoter, injection of the Gal4/UAS-Aβ42 trimer induced high levels of Aβ42 antigen expression in tissue suggesting a mechanism for the increase in anti-Aβ42 antibody. Antibodies were found to be primarily IgG1 suggesting a predominant Th2 response (IgG1/IgG2a ratio of 9). Serum from Aβ42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. These results demonstrate the potential therapeutic use of Gal4/UAS DNA Aβ42 trimer immunization in preventing Alzheimer's disease.

AB - In an effort to optimize DNA immunization-elicited antibody production responses against Aβ1-42 (Aβ42) as a therapy for Alzheimer's disease (AD), comparisons were made between three distinct plasmid systems using gene gun delivery. Plasmids encoding Aβ42 monomer and a novel Aβ42 trimeric fusion protein were evaluated in conjunction with CMV or Gal4/UAS promoter elements. It was found that vaccination Aβ42 trimer under the Gal4/UAS promoter elicited high levels of anti-Aβ42 antibody production. Serum antibody levels from Gal4/UAS-Aβ42 trimer immunized mice were found to be 16.6 ± 5.5 μg/ml compared to 6.5 ± 2.5 μg/ml with Gal4/UAS-Aβ42 monomer or even less with CMV-Aβ42 trimer. As compared to monomeric Aβ42 or Aβ42 trimer expressed under the CMV promoter, injection of the Gal4/UAS-Aβ42 trimer induced high levels of Aβ42 antigen expression in tissue suggesting a mechanism for the increase in anti-Aβ42 antibody. Antibodies were found to be primarily IgG1 suggesting a predominant Th2 response (IgG1/IgG2a ratio of 9). Serum from Aβ42 trimer-vaccinated mice was also found to identify amyloid plaques in the brains of APP/PS1 transgenic mice. These results demonstrate the potential therapeutic use of Gal4/UAS DNA Aβ42 trimer immunization in preventing Alzheimer's disease.

KW - Alzheimer's disease

KW - Aβ42 peptide

KW - DNA Aβ42 immunization

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