Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-β (Aβ) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel Aβ B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 × Tg-AD mice. Using a toxin-derived carrier protein, the rCV02 vaccine elicited robust Aβ-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 × Tg-AD mice. Along with the behavioral improvement in aged 3 × Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Aβ or oligomeric forms of Aβ, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Aβ levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Aβ-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine.
Highlights
Alzheimer’s disease (AD) is characterized by senile plaques (SPs) and neurofibrillary tangles (NFTs)
Lymphocyte proliferative responses showed that rCV02 induced THc-specific responses, but not Aβ-specific T cell immunity in immunized mice (Fig. 1B, p < 0.05) and significantly increased IL-4 (Th2) or IFN-γ(Th1) cytokine levels induced by THc but not by Aβ42 (Fig. 1C,D, p < 0.01)
The objective of this study was to undertake a comprehensive evaluation of the immunopotency of a novel clinical grade epitope immunogen 6Aβ15–THc-C formulated with alum adjuvant in 3 ×Tg-AD mice and to determine the subsequent effects on Aβ-related pathologies and cognition
Summary
Alzheimer’s disease (AD) is characterized by senile plaques (SPs) and neurofibrillary tangles (NFTs). Given the remarkable recovery of cognition in AD models of targeted-Aβimmunotherapy, it is necessary to determine the molecular correlations associated with improvement. Splenocytes were harvested from rCV02immunized and control mice and restimulated in vitro with 10 μg/mL Aβ42 and THc. Cytokine production from splenocytes was used as a surrogate marker of Th1 (IFN-γ; (E)) and Th2 (IL-4; (D)) bias in the immune response to rCV02. Models of AD remains to be clarified In this study, this recombinant chimeric 6Aβ15-THc-C immunogen was formulated with alum adjuvant as a novel AβB-cell epitope candidate vaccine (rCV02). We sought to determine the molecular correlations between the recovery of cognition and the improvement of synaptic functions. The immune mechanism associated with rCV02 vaccination with the aid of a toxin-derived carrier was defined in 3 ×Tg-AD mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
