DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.

Research output: Contribution to journalArticle

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

The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that Aβ42 DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to Aβ42 peptide re-stimulation was absent in DNA Aβ42 trimer-immunized mice when compared to Aβ42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with Aβ42 trimer DNA and Aβ42 peptide with Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the Aβ42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response and no IFNγ or IL-17 secretion after Aβ42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen Aβ42 in brain. Therefore, Aβ42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.

Original languageEnglish (US)
Pages (from-to)867-874
Number of pages8
JournalCellular and Molecular Neurobiology
Volume31
Issue number6
StatePublished - 2011

PMID: 21625960

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DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation. / Lambracht-Washington, Doris; Qu, Bao Xi; Fu, Min; Anderson, Larry D.; Stüve, Olaf; Eagar, Todd N.; Rosenberg, Roger N.

In: Cellular and Molecular Neurobiology, Vol. 31, No. 6, 2011, p. 867-874.

Research output: Contribution to journalArticle

Harvard

Lambracht-Washington, D, Qu, BX, Fu, M, Anderson, LD, Stüve, O, Eagar, TN & Rosenberg, RN 2011, 'DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.' Cellular and Molecular Neurobiology, vol. 31, no. 6, pp. 867-874.

APA

Lambracht-Washington, D., Qu, B. X., Fu, M., Anderson, L. D., Stüve, O., Eagar, T. N., & Rosenberg, R. N. (2011). DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation. Cellular and Molecular Neurobiology, 31(6), 867-874.

Vancouver

Lambracht-Washington D, Qu BX, Fu M, Anderson LD, Stüve O, Eagar TN et al. DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation. Cellular and Molecular Neurobiology. 2011;31(6):867-874.

Author

Lambracht-Washington, Doris ; Qu, Bao Xi ; Fu, Min ; Anderson, Larry D. ; Stüve, Olaf ; Eagar, Todd N. ; Rosenberg, Roger N. / DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation. In: Cellular and Molecular Neurobiology. 2011 ; Vol. 31, No. 6. pp. 867-874.

BibTeX

@article{64a140fc66a84f83af755e99f89d83bc,
title = "DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.",
abstract = "The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42 peptide was stopped when 6{\%} of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that Aβ42 DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to Aβ42 peptide re-stimulation was absent in DNA Aβ42 trimer-immunized mice when compared to Aβ42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with Aβ42 trimer DNA and Aβ42 peptide with Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the Aβ42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response and no IFNγ or IL-17 secretion after Aβ42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen Aβ42 in brain. Therefore, Aβ42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.",
author = "Doris Lambracht-Washington and Qu, {Bao Xi} and Min Fu and Anderson, {Larry D.} and Olaf St{\"u}ve and Eagar, {Todd N.} and Rosenberg, {Roger N.}",
year = "2011",
language = "English (US)",
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journal = "Cellular and Molecular Neurobiology",
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RIS

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T1 - DNA immunization against amyloid beta 42 has high potential as safe therapy for Alzheimer's disease as it diminishes antigen-specific Th1 and Th17 cell proliferation.

AU - Lambracht-Washington, Doris

AU - Qu, Bao Xi

AU - Fu, Min

AU - Anderson, Larry D.

AU - Stüve, Olaf

AU - Eagar, Todd N.

AU - Rosenberg, Roger N.

PY - 2011

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N2 - The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that Aβ42 DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to Aβ42 peptide re-stimulation was absent in DNA Aβ42 trimer-immunized mice when compared to Aβ42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with Aβ42 trimer DNA and Aβ42 peptide with Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the Aβ42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response and no IFNγ or IL-17 secretion after Aβ42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen Aβ42 in brain. Therefore, Aβ42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.

AB - The pathogenesis of Alzheimer's disease (AD) has been strongly associated with the accumulation of amyloid beta (Aβ) peptides in brain, and immunotherapy targeting Aβ provides potential for AD prevention. A clinical trial in which AD patients were immunized with Aβ42 peptide was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response. Previously, we and other have shown that Aβ42 DNA vaccination via gene gun generates a Th2 cellular immune response, which was shown by analyses of the respective antibody isotype profiles. We also determined that in vitro T cell proliferation in response to Aβ42 peptide re-stimulation was absent in DNA Aβ42 trimer-immunized mice when compared to Aβ42 peptide-immunized mice. To further characterize this observation prospectively and longitudinally, we analyzed the immune response in wild-type mice after vaccination with Aβ42 trimer DNA and Aβ42 peptide with Quil A adjuvant. Wild-type mice were immunized with short-term (1-3× vaccinations) or long-term (6× vacinations) immunization strategies. Antibody titers and isotype profiles of the Aβ42 specific antibodies, as well as cytokine profiles and cell proliferation studies from this longitudinal study were determined. Sufficient antibody titers to effectively reduce Aβ42, but an absent T cell proliferative response and no IFNγ or IL-17 secretion after Aβ42 DNA trimer immunization minimizes the risk of inflammatory activities of the immune system towards the self antigen Aβ42 in brain. Therefore, Aβ42 DNA trimer immunization has a high probability to be effective and safe to treat patients with early AD.

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