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• W2023551175 abstract "The antibodies to the beta-amyloid (Aβ) peptide endows therapeutic effects in Alzheimer's disease both in pre-clinical and clinical settings. This approach is currently hampered by elicitation of pathological autoreactivity. In order to overcome this problem,we have developed several strategies to limit generation of autoreactive Th cells. For example, we first reported generation of an epitope vaccine composed of small immunodominant self B cell epitope of Aβ42 fused with a foreign promiscous CD4+Th cell epitope, PADRE, which induced high titers of anti-Aβ antibodies without generation of potentially harmful autoreactive T cells. Importantly, these antibodies were therapeutically active, as we showed in two different mouse models of AD, APP/Tg 2576 and 3xTg-AD. After having demonstrated feasibility of antibody response to Aβ in the absence of autoreactive Th cells, we suggested that in humans anti-Aβ antibody could be safer if they will be generated in pre-symptomatic people. More specifically, we hypothesized that in these people who did not develop yet significant deposits of toxic species of Aβ in the brains anti-Aβ antibodies may not induce microhemorrhages. In order to test this hypothesis, we decided to use the influenza virus platform for delivery of immunodominant B cell epitopes of Aβ42 (Aβ1–10) into the host. We demonstrated that such dual vaccine activates only anti-viral Th cells and induces robust anti-Aβ and anti-influenza antibodies in wild-type and APP/Tg mice. Currently, we are testing the ability of APP/Tg mice previously vaccinated with influenza vaccine, as opposed to non-influenza-vaccinated animals, promote more rapid and potent anti-Aβ antibody production when boosted once with dual vaccine. In other words, we are investigating the role of pre-existing anti-viral memory Th cells in rapid and efficient generation of anti-Aβ antibody responses in APP/Tg mice. As we suggested, these experiments could simulate the situation in people with early pre-clinical stage AD repeatedly vaccinated/infected with flu virus. Importantly, if successful, dual-vaccine can be used in people with AD at a very early stage that can be diagnosed by measuring tau/Aβ and ptau/Aβ ratio in CSF and/or by screening for accumulation of Aβ in the brains using PIB-PET scan." @default.
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• W2023551175 date "2008-07-01" @default.
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• W2023551175 title "P2-298: The novel strategy for generation of effective and safe Alzheimer's disease vaccine based on conventional influenza virus vaccine modified to express Aβ1-11" @default.
• W2023551175 doi "https://doi.org/10.1016/j.jalz.2008.05.1374" @default.
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