Dual Vaccine Shows Promise for Treating Alzheimer’s in Early Study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A dual vaccine targeting both amyloid plaques and tangled fibers made up of tau — two abnormal protein aggregates that build up in the brain of those with Alzheimer’s — may have potential to treat and prevent the disease.

Prothena, its developer, has found preclinical evidence that the vaccine drives the generation of a sufficient amount of antibodies that are able to bind to and neutralize both amyloid and tau proteins, with reasonable safety.

These characteristics are hard to find and have previously prevented the development of safe and effective vaccines for Alzheimer’s.

“The need for vaccines to prevent Alzheimer’s … from ever occurring is urgent,” Wagner M. Zago, PhD, chief scientific officer of Prothena, said in a press release.

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Zago presented the findings in an oral presentation, titled “Development of a dual Aβ/tau vaccine for the treatment and prevention of Alzheimer’s disease,” at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2022), which was held March 15–20 in Barcelona, Spain, and virtually.

With this preclinical data, the company plans to file an investigational new drug (IND) application to test the candidate vaccine in human trials.

“Data presented at AD/PD builds momentum for Prothena’s planned IND filing for an Alzheimer’s vaccine candidate in 2023,” the company wrote in an email to Alzheimer’s News Today.

Prothena’s investigational vaccine consists of short protein chains, called linear peptides, designed to prevent the formation of amyloid plaques and tau tangles. 

Studies in multiple animal species revealed that the vaccine is able to generate an immune response of appropriate magnitude. In other words, the vaccine was able to trigger a robust and balanced response with antibodies against both amyloid and tau proteins.

The antibodies were able to inhibit the binding of soluble amyloid-beta aggregates to nerve cells (neurons) grown in a dish in the laboratory (in vitro) and were able to bind to amyloid plaques and tau tangles in slices of brain tissue from patients with Alzheimer’s, at amounts expected to be achieved in the central nervous system in vivo.

They also induced clearance of amyloid protein and blocked the binding of tau protein to heparin, an analog of heparan sulfate. Binding of tau to heparan sulfate is believed to play a role in how tau spreads and moves within nerve cells.

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Safety was studied in non-human primates. Several immunizations with the vaccine did not result in cytotoxic T-cell responses to amyloid beta or tau proteins. In other words, the vaccine did not generate a potentially dangerous and exacerbated immune response in these animals.

“Our dual Aβ/tau vaccine demonstrated, in a preclinical setting, simultaneous generation of antibodies against [amyloid] and tau with the proper quantity and quality of response, while avoiding engagement of cytotoxic immune responses,” Zago said.

The researchers wrote in their presentation: “These preclinical data support clinical development of this dual-immunogen vaccine for the potential treatment and/or prevention of Alzheimer’s disease.”