Loke Diagnostics ApS

Denmark

Loke Diagnostics ApS

Denmark
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Axelsen T.V.,Loke Diagnostics ApS | Axelsen T.V.,University of Aarhus | Holm A.,Loke Diagnostics ApS | Christiansen G.,Loke Diagnostics ApS | Birkelund S.,Loke Diagnostics ApS
Vaccine | Year: 2011

Alzheimer's disease (AD) is characterized by neurofibrillary tangles, consisting of hyperphosphorylated tau protein and senile plaques, which are consisting mainly of amyloid-β (Aβ). Attempts to generate a safe vaccine against Aβ rely on both B- and T-cell epitopes within the neurotoxic peptide Aβ1-42. This, however, poses a risk for an inflammatory and/or autoimmune response against Aβ-peptides in the brain. To overcome such risks we wanted to identify the shortest C-terminal Aβ-peptide that would induce antibodies selectively recognizing the C-terminal end of Aβ42. Immunization with this antigen should result in a non-inflammatory Th2 immune response and the T-cell response should be against a T-cell epitope covalently attached to the small Aβ-peptide. Antigen constructs were made by the ligand presenting assembly (LPA) technology, comprising dimeric presentation of short Aβ-peptides ending at amino acid 42 in connection with potent T-cell epitopes. Mice were immunized with antigen constructs using different adjuvants, and sera from mice were tested to characterize the generated immune response. Immunization with Keyhole limpet hemocyanin (KLH)-Aβ 37-42 resulted in generation of IgG1 antibodies specific for the Aβ42 C-terminal end, indicating a Th2-response. The T-cell mediated response was predominantly against T-cell epitopes in KLH. The antibodies stained senile plaques specifically in brain tissue from AD patients. Thus, KLH-Aβ 37-42 was able to induce a non-inflammatory and highly specific antibody response against Aβ42. © 2011 Elsevier Ltd.

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