DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model

Research output: Contribution to journalArticle

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

Context: DNA β-amyloid1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (TH2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Aβ42 peptide that occur in the brain of patients with AD. Objective: To compare the immune response in wild-type mice after immunization with DNA Aβ42 trimer and Aβ42 peptide. Design and Intervention: Wild-type mice received either 4 μ g of DNA Aβ42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 μ g of human Aβ42 peptide with the adjuvant Quil A (n=8). Titers, epitope mapping, and isotypes of the Aβ42-specific antibodies were analyzed. Main Outcome Measures: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Aβ42-specific antibodies, and T-cell activation. Results: DNA Aβ42 trimer immunization resulted in antibody titers with a mean of 15 μ g per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a TH2 type of immune response (IgG1/IgG2a ratio of 10). The peptideimmunized mice showed a mixed TH1/TH2 immune response (IgG1/IgG2a ratio of 1) (P<.001). No increased T-cell proliferation was observed in the DNA-immunized mice (P=.03). Conclusion: In this preliminary study in a wild-type mouse model, DNA Aβ42 trimer immunization protocol produced a TH2 immune response and appeared to have low potential to cause an inflammatory T-cell response.

Original languageEnglish (US)
Pages (from-to)1796-1802
Number of pages7
JournalJAMA - Journal of the American Medical Association
Volume302
Issue number16
DOIs
StatePublished - Dec 16 2009

PMID: 19861672

PMCID: PMC2896011

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DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model. / Lambracht-Washington, Doris; Qu, Bao Xi; Fu, Min; Eagar, Todd N.; Stüve, Olaf; Rosenberg, Roger N.

In: JAMA - Journal of the American Medical Association, Vol. 302, No. 16, 16.12.2009, p. 1796-1802.

Research output: Contribution to journalArticle

Harvard

Lambracht-Washington, D, Qu, BX, Fu, M, Eagar, TN, Stüve, O & Rosenberg, RN 2009, 'DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model' JAMA - Journal of the American Medical Association, vol. 302, no. 16, pp. 1796-1802. https://doi.org/10.1001/jama.2009.1547

APA

Lambracht-Washington, D., Qu, B. X., Fu, M., Eagar, T. N., Stüve, O., & Rosenberg, R. N. (2009). DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model. JAMA - Journal of the American Medical Association, 302(16), 1796-1802. https://doi.org/10.1001/jama.2009.1547

Vancouver

Lambracht-Washington D, Qu BX, Fu M, Eagar TN, Stüve O, Rosenberg RN. DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model. JAMA - Journal of the American Medical Association. 2009 Dec 16;302(16):1796-1802. https://doi.org/10.1001/jama.2009.1547

Author

Lambracht-Washington, Doris ; Qu, Bao Xi ; Fu, Min ; Eagar, Todd N. ; Stüve, Olaf ; Rosenberg, Roger N. / DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model. In: JAMA - Journal of the American Medical Association. 2009 ; Vol. 302, No. 16. pp. 1796-1802.

BibTeX

@article{ef919951e32544e8b4c032e2b2aecbaa,
title = "DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model",
abstract = "Context: DNA β-amyloid1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (TH2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Aβ42 peptide that occur in the brain of patients with AD. Objective: To compare the immune response in wild-type mice after immunization with DNA Aβ42 trimer and Aβ42 peptide. Design and Intervention: Wild-type mice received either 4 μ g of DNA Aβ42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 μ g of human Aβ42 peptide with the adjuvant Quil A (n=8). Titers, epitope mapping, and isotypes of the Aβ42-specific antibodies were analyzed. Main Outcome Measures: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Aβ42-specific antibodies, and T-cell activation. Results: DNA Aβ42 trimer immunization resulted in antibody titers with a mean of 15 μ g per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a TH2 type of immune response (IgG1/IgG2a ratio of 10). The peptideimmunized mice showed a mixed TH1/TH2 immune response (IgG1/IgG2a ratio of 1) (P<.001). No increased T-cell proliferation was observed in the DNA-immunized mice (P=.03). Conclusion: In this preliminary study in a wild-type mouse model, DNA Aβ42 trimer immunization protocol produced a TH2 immune response and appeared to have low potential to cause an inflammatory T-cell response.",
author = "Doris Lambracht-Washington and Qu, {Bao Xi} and Min Fu and Eagar, {Todd N.} and Olaf St{\"u}ve and Rosenberg, {Roger N.}",
year = "2009",
month = "12",
day = "16",
doi = "10.1001/jama.2009.1547",
language = "English (US)",
volume = "302",
pages = "1796--1802",
journal = "JAMA: The Journal of the American Medical Association",
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RIS

TY - JOUR

T1 - DNA β-amyloid1-42 trimer immunization for alzheimer diseaseina wild-type mouse model

AU - Lambracht-Washington, Doris

AU - Qu, Bao Xi

AU - Fu, Min

AU - Eagar, Todd N.

AU - Stüve, Olaf

AU - Rosenberg, Roger N.

PY - 2009/12/16

Y1 - 2009/12/16

N2 - Context: DNA β-amyloid1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (TH2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Aβ42 peptide that occur in the brain of patients with AD. Objective: To compare the immune response in wild-type mice after immunization with DNA Aβ42 trimer and Aβ42 peptide. Design and Intervention: Wild-type mice received either 4 μ g of DNA Aβ42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 μ g of human Aβ42 peptide with the adjuvant Quil A (n=8). Titers, epitope mapping, and isotypes of the Aβ42-specific antibodies were analyzed. Main Outcome Measures: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Aβ42-specific antibodies, and T-cell activation. Results: DNA Aβ42 trimer immunization resulted in antibody titers with a mean of 15 μ g per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a TH2 type of immune response (IgG1/IgG2a ratio of 10). The peptideimmunized mice showed a mixed TH1/TH2 immune response (IgG1/IgG2a ratio of 1) (P<.001). No increased T-cell proliferation was observed in the DNA-immunized mice (P=.03). Conclusion: In this preliminary study in a wild-type mouse model, DNA Aβ42 trimer immunization protocol produced a TH2 immune response and appeared to have low potential to cause an inflammatory T-cell response.

AB - Context: DNA β-amyloid1-42 (Aβ42) trimer immunization was developed to produce specific T helper 2 cell (TH2)-type antibodies to provide an effective and safe therapy for Alzheimer disease (AD) by reducing elevated levels of Aβ42 peptide that occur in the brain of patients with AD. Objective: To compare the immune response in wild-type mice after immunization with DNA Aβ42 trimer and Aβ42 peptide. Design and Intervention: Wild-type mice received either 4 μ g of DNA Aβ42 trimer immunization administered with gene gun (n=8) or intraperitoneal injection of 100 μ g of human Aβ42 peptide with the adjuvant Quil A (n=8). Titers, epitope mapping, and isotypes of the Aβ42-specific antibodies were analyzed. Main Outcome Measures: Antibody titers, mapping of binding sites (epitopes), isotype profiles of the Aβ42-specific antibodies, and T-cell activation. Results: DNA Aβ42 trimer immunization resulted in antibody titers with a mean of 15 μ g per milliliter of plasma. The isotype profile of the antibodies differed markedly. A predominant IgG1 antibody response was found in the DNA-immunized mice, indicating a TH2 type of immune response (IgG1/IgG2a ratio of 10). The peptideimmunized mice showed a mixed TH1/TH2 immune response (IgG1/IgG2a ratio of 1) (P<.001). No increased T-cell proliferation was observed in the DNA-immunized mice (P=.03). Conclusion: In this preliminary study in a wild-type mouse model, DNA Aβ42 trimer immunization protocol produced a TH2 immune response and appeared to have low potential to cause an inflammatory T-cell response.

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DO - 10.1001/jama.2009.1547

M3 - Article

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EP - 1802

JO - JAMA: The Journal of the American Medical Association

T2 - JAMA: The Journal of the American Medical Association

JF - JAMA: The Journal of the American Medical Association

SN - 0098-7484

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