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Cage Fighting with Dementia: Bioengineering protein cages into a next-generation vaccine against Alzheimer’s Disease

Project Member(s): Care, A., Boyton, I., Saunders, B.

Funding or Partner Organisation: Dementia Australia Research Foundation Ltd
Dementia Australia Research Foundation Ltd

Start year: 2023

Summary: Alzheimer's disease (AD) is characterized by abnormal aggregations of two proteins in the brain: β-amyloid (Aβ) and hyperphosphorylated tau (pTau). As these aggregations increase over time, so does the cognitive decline in patients. Clinically-approved AD treatments are limited to intravenously administered monoclonal antibodies (mABs) that mark amyloid-β (Aβ) plaques in the brain for degradation by the immune system. However, serious concerns have been raised about the therapeutic efficacy, safety, and cost of these mABs. The goal of this project is to develop a next-generation AD vaccine that simultaneously targets both abnormal Aβ and pTau. Our hypothesis is that natural protein nanocages can be bioengineered to display and deliver both Aβ and pTau antigens, stimulating the body to produce its own antibodies against both targets, enabling their removal from the brain. We will have three aims: (1) bioengineering the nanocages to display Aβ and pTau antigens, (2) evaluating the vaccine's ability to induce antibody generation against both antigens in vivo, and (3) testing the therapeutic efficacy of the vaccine in an AD animal model. The significance of this project lies in the potential of active immunotherapy as a cheaper, safer, and more convenient alternative to mABs, and the use of a modular encapsulin-based vaccine for targeting multiple pathological forms of Aβ and pTau. Our preliminary data shows that we can make a nanocage vaccine that induces the production antibodies that recognises AD-specific antigens. Overall, this project aims to provide an AD vaccine that safe, effective, cheap and accessible to everyone.

FOR Codes: Nanomedicine, Neurosciences, Synthetic biology, Preventive medicine , Treatment of human diseases and conditions, Human pharmaceutical treatments , Expanding knowledge in the biomedical and clinical sciences