Vaccine Drives Antibodies to Target Tau Tangles in Mice

Alzheimer’s disease is a progressive memory disorder that affects nearly one in three seniors and is on the rise, currently affecting 43 million people worldwide.         

Behind the memory impairments, there is a perfect storm of destruction in the brain, stemming in part from accumulations of a protein called tau. Normally a stabilizing structure inside of neurons, tau can accumulate in long tangles that disrupt the ability of neurons to communicate with one another.

University of New Mexico researchers have developed a vaccine that could prevent the formation of the tau tangles and potentially prevent the cognitive decline typically seen in Alzheimer’s patients.

In a paper published last week in NPJ Vaccines, the team reported it had engineered a vaccine using virus-like particles (VLPs, for short) that eliminated the tau tangles in mice that had been bred to develop symptoms like those affecting human Alzheimer’s patients.

“We’re excited by these findings, because they seem to suggest that we can use the body’s own immune system to make antibodies against these tangles, and that these antibodies actually bind and clear these tau tangles,” said Nicole Maphis, a PhD candidate in UNM’s Biomedical Sciences Graduate Program.

Maphis, working in the lab of Kiran Bhaskar, PhD, an associate professor in UNM’s Department of Molecular Genetics & Microbiology, found that when the vaccine was given to mice, they developed antibodies that cleared the tau protein from their brains – and the response lasted for months.

Then, she tested the animals in a battery of maze-like tests. Mice receiving the vaccination performed remarkably better than those that hadn’t. MRI scans showed that the vaccinated animals had less brain shrinkage, suggesting that the vaccine prevented neurons from dying.

Maphis also found significantly fewer tangles in both the cortex and the hippocampus – areas in the brain that are important for learning and memory, and which are destroyed in Alzheimer’s.

“These results confirm that targeting tau tangles using a vaccine intervention could rescue memory impairments and prevent neurons from dying,” Maphis said.

The vaccine was created with help from UNM scientists David Peabody and Bryce Chackerian. The pair helped pioneer the use of VLPs to create vaccines targeting dengue virus, hepatitis B, human papillomavirus and amyloid beta protein (which is also present in the brains of Alzheimer’s patients).

VLPs are derived from viruses that have their genomes removed, leaving only their outer protein shell. Lacking a genome, they’re unable to reproduce, but the body’s immune system still recognizes them as foreign invaders and manufactures antibodies to neutralize the proteins attached to their surface. In this case, a portion of tau protein on the surface of the VLP triggers an immune response, leading to the elimination of the tau tangles.

Going forward, Bhaskar hopes to obtain funding to commercialize this vaccine in order to create an injection that could potentially be tested in human patients. However, moving a drug from bench to bedside can cost millions of dollars and take decades.

By partnering with AgilVax, Inc., a company formed to commercialize the VLP technology, and STC.UNM (UNM’s technology commercialization arm), Bhaskar hopes to receive funding from a federal Small Business Innovation Research grant to help move the research project forward.

Reference:

Maphis, N. M., Peabody, J., Crossey, E., Jiang, S., Ahmad, F. A. J., Alvarez, M., … Bhaskar, K. (2019). Qß Virus-like particle-based vaccine induces robust immunity and protects against tauopathy. Npj Vaccines, 4(1), 2. https://doi.org/10.1038/s41541-019-0118-4

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