A noninflammatory immune response in aged DNA Aβ42-immunized mice supports its safety for possible use as immunotherapy in AD patients

Neurobiology of Aging
Doris Lambracht-Washington, Roger N Rosenberg

Abstract

Aging in the immune system results in tendency to proinflammatory responses. Intradermal DNA immunization showed Th2 polarized noninflammatory immune responses. We tested here 18-month-old mice which were immunized with Aβ42 peptide, DNA Aβ42 trimer, or 2 different prime boost protocols identical to previous experiments. High Aβ42 antibody levels were found in aged mice which had received peptide immunizations (900 μg/mL plasma), and in mice which had received peptide prime and DNA boost immunizations (500 μg/mL), compared with antibodies in DNA Aβ42 immunized mice with 50 μg/mL. Although we found T-cell proliferation and inflammatory cytokines in mice which had received peptide or prime boost immunization, these were not found in DNA-immunized mice. The results are concordant with proinflammatory responses because of immunosenescence and contraindicate the use of Aβ42 peptide immunizations or prime boost immunization protocols for the use in elderly Alzheimer's disease patients. DNA Aβ42 immunization only on the other hand does lead to effective levels of antibodies without inflammatory cytokine or T-cell responses in the aged animal model tested.

References

Aug 28, 1998·Mechanisms of Ageing and Development·L RinkH Kirchner
Feb 26, 2000·Vaccine·M E Weksler
May 3, 2000·Clinical and Experimental Immunology·S Sakata-KanekoT Kita
May 11, 2005·Neurology·S GilmanUNKNOWN AN1792(QS-21)-201 Study Team
May 11, 2005·Neurology·N C FoxUNKNOWN AN1792(QS-21)-201 Study
Sep 10, 2005·Vaccine·Robert J DrapeHansi J Dean
Mar 25, 2006·Journal of the Neurological Sciences·Baoxi QuRoger N Rosenberg
Nov 23, 2006·Mechanisms of Ageing and Development·Claudio FranceschiStefano Salvioli
Jan 4, 2007·The Journal of Pathology·A L GruverG D Sempowski
Jun 19, 2007·Journal of the Neurological Sciences·Bao-Xi QuRoger N Rosenberg
Sep 18, 2007·Neurobiology of Aging·Andrew J Farrall, Joanna M Wardlaw
Jan 2, 2008·Experimental Gerontology·Peter UciechowskiLothar Rink
Mar 8, 2008·Expert Review of Vaccines·Shan LuJill M Grimes-Serrano
Oct 11, 2008·Expert Review of Vaccines·Jean-François Nicolas, Bruno Guy
Mar 7, 2009·Journal of the Neurological Sciences·Bogdan O PopescuNenad Bogdanovic
Jun 23, 2009·Trends in Immunology·Wilbur H ChenMarcelo B Sztein
Oct 29, 2009·JAMA : the Journal of the American Medical Association·Doris Lambracht-WashingtonRoger N Rosenberg
Jun 12, 2010·Annals of the New York Academy of Sciences·Tamas FulopAnis Larbi
Mar 26, 2011·Nature Reviews. Immunology·Arne N Akbar, Sian M Henson
Jun 28, 2011·Current Opinion in Immunology·Milica Vukmanovic-StejicArne N Akbar
Sep 24, 2013·Experimental Gerontology·Vanessa SchmittPeter Uciechowski
Dec 12, 2013·Aging Cell·Sanjay K GargRaymond Yung
May 17, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Claudio Franceschi, Judith Campisi

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Citations

Jan 29, 2016·Expert Opinion on Emerging Drugs·Daniela Galimberti, Elio Scarpini
Nov 21, 2018·Alzheimer's Research & Therapy·Roger N RosenbergDoris Lambracht-Washington

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