A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

Research output: Contribution to journalArticle

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

Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalJournal of Neuroimmunology
Volume254
Issue number1-2
DOIs
StatePublished - Jan 15 2013

PMID: 23036592

PMCID: PMC4084825

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A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. / Lambracht-Washington, Doris; Qu, Bao Xi; Fu, Min; Anderson, Larry D.; Eagar, Todd N.; Stüve, Olaf; Rosenberg, Roger N.

In: Journal of Neuroimmunology, Vol. 254, No. 1-2, 15.01.2013, p. 63-68.

Research output: Contribution to journalArticle

Harvard

Lambracht-Washington, D, Qu, BX, Fu, M, Anderson, LD, Eagar, TN, Stüve, O & Rosenberg, RN 2013, 'A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease' Journal of Neuroimmunology, vol. 254, no. 1-2, pp. 63-68. https://doi.org/10.1016/j.jneuroim.2012.09.008

APA

Lambracht-Washington, D., Qu, B. X., Fu, M., Anderson, L. D., Eagar, T. N., Stüve, O., & Rosenberg, R. N. (2013). A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. Journal of Neuroimmunology, 254(1-2), 63-68. https://doi.org/10.1016/j.jneuroim.2012.09.008

Vancouver

Lambracht-Washington D, Qu BX, Fu M, Anderson LD, Eagar TN, Stüve O et al. A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. Journal of Neuroimmunology. 2013 Jan 15;254(1-2):63-68. https://doi.org/10.1016/j.jneuroim.2012.09.008

Author

Lambracht-Washington, Doris ; Qu, Bao Xi ; Fu, Min ; Anderson, Larry D. ; Eagar, Todd N. ; Stüve, Olaf ; Rosenberg, Roger N. / A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. In: Journal of Neuroimmunology. 2013 ; Vol. 254, No. 1-2. pp. 63-68.

BibTeX

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title = "A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease",
abstract = "Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6{\%} of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use.",
keywords = "Alzheimer disease, Amyloid beta 1-42, Antibody production, DNA vaccination, Immunotherapy, Regulatory immune response",
author = "Doris Lambracht-Washington and Qu, {Bao Xi} and Min Fu and Anderson, {Larry D.} and Eagar, {Todd N.} and Olaf St{\"u}ve and Rosenberg, {Roger N.}",
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T1 - A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease

AU - Lambracht-Washington, Doris

AU - Qu, Bao Xi

AU - Fu, Min

AU - Anderson, Larry D.

AU - Eagar, Todd N.

AU - Stüve, Olaf

AU - Rosenberg, Roger N.

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N2 - Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use.

AB - Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use.

KW - Alzheimer disease

KW - Amyloid beta 1-42

KW - Antibody production

KW - DNA vaccination

KW - Immunotherapy

KW - Regulatory immune response

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