BACKGROUND: One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral vessels. Immunization of AD mouse models with Abeta reduces Abeta deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Abeta were halted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmune response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed. METHODS: We have nasally immunized a young AD mouse model with an adenovirus vector encoding 11 tandem repeats of Abeta1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Abeta1-6)(11), in order to evaluate the efficacy of the vector in preventing Abeta deposits in the brain. We also have investigated immune responses of mice to AdPEDI-(Abeta1-6)(11). RESULTS: Nasal immunization of an AD mouse model with AdPEDI-(Abeta1-6)(11) elicited a predominant IgG1 response and reduced Abeta load in the brain. The plasma IL-10 level in the AD mouse model was upregulated after immunization and, upon the stimulation with PEDI-(Abeta1-6)(11), marked IL-10 responses were found in splenic CD4(+) T cells from C57BL/6 mice that had been immunized with AdPEDI-(Abeta1-6)(11). CONCLUSIONS: These results suggest that the induction of Th2-biased responses with AdPEDI-(Abeta1-6)(11) in mice is mediated in part through the upregulation of IL-10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells. Copyright (c) 2007 John Wiley & Sons, Ltd.
BACKGROUND: One of the pathological hallmarks of Alzheimer's disease (AD) is deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral vessels. Immunization of ADmouse models with Abeta reduces Abeta deposits and improves memory and learning deficits. Because recent clinical trials of immunization with Abeta were halted due to brain inflammation that was presumably induced by a T-cell-mediated autoimmune response, vaccination modalities that elicit predominantly humoral immune responses are currently being developed. METHODS: We have nasally immunized a young ADmouse model with an adenovirus vector encoding 11 tandem repeats of Abeta1-6 fused to the receptor-binding domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Abeta1-6)(11), in order to evaluate the efficacy of the vector in preventing Abeta deposits in the brain. We also have investigated immune responses of mice to AdPEDI-(Abeta1-6)(11). RESULTS: Nasal immunization of an ADmouse model with AdPEDI-(Abeta1-6)(11) elicited a predominant IgG1 response and reduced Abeta load in the brain. The plasma IL-10 level in the ADmouse model was upregulated after immunization and, upon the stimulation with PEDI-(Abeta1-6)(11), marked IL-10 responses were found in splenic CD4(+) T cells from C57BL/6 mice that had been immunized with AdPEDI-(Abeta1-6)(11). CONCLUSIONS: These results suggest that the induction of Th2-biased responses with AdPEDI-(Abeta1-6)(11) in mice is mediated in part through the upregulation of IL-10, which inhibits activation of dendritic cells that dictate the induction of Th1 cells. Copyright (c) 2007 John Wiley & Sons, Ltd.
Authors: Christine Rollier; Ernst J Verschoor; Glaucia Paranhos-Baccala; Joost A R Drexhage; Babs E Verstrepen; Jean-Luc Berland; Nourredine Himoudi; Christina Barnfield; Peter Liljestrom; Juan Jose Lasarte; Juan Ruiz; Genevieve Inchauspe; Jonathan L Heeney Journal: J Infect Dis Date: 2005-08-01 Impact factor: 5.226
Authors: Margaret M Racke; Laura I Boone; Deena L Hepburn; Maia Parsadainian; Matthew T Bryan; Daniel K Ness; Kathy S Piroozi; William H Jordan; Donna D Brown; Wherly P Hoffman; David M Holtzman; Kelly R Bales; Bruce D Gitter; Patrick C May; Steven M Paul; Ronald B DeMattos Journal: J Neurosci Date: 2005-01-19 Impact factor: 6.167
Authors: Margaret Liu; Bruce Acres; Jean-Marc Balloul; Nadine Bizouarne; Stephane Paul; Philippe Slos; Patrick Squiban Journal: Proc Natl Acad Sci U S A Date: 2004-08-27 Impact factor: 11.205
Authors: D Games; D Adams; R Alessandrini; R Barbour; P Berthelette; C Blackwell; T Carr; J Clemens; T Donaldson; F Gillespie Journal: Nature Date: 1995-02-09 Impact factor: 49.962
Authors: J Xu-Amano; H Kiyono; R J Jackson; H F Staats; K Fujihashi; P D Burrows; C O Elson; S Pillai; J R McGhee Journal: J Exp Med Date: 1993-10-01 Impact factor: 14.307
Authors: Doris Lambracht-Washington; Bao-Xi Qu; Min Fu; Todd N Eagar; Olaf Stüve; Roger N Rosenberg Journal: JAMA Date: 2009-10-28 Impact factor: 56.272
Authors: Doris Lambracht-Washington; Bao-Xi Qu; Min Fu; Larry D Anderson; Olaf Stüve; Todd N Eagar; Roger N Rosenberg Journal: Cell Mol Neurobiol Date: 2011-04-06 Impact factor: 5.046
Authors: Bao-Xi Qu; Doris Lambracht-Washington; Min Fu; Todd N Eagar; Olaf Stüve; Roger N Rosenberg Journal: Vaccine Date: 2010-06-04 Impact factor: 3.641