A New Vaccine Design That Could be Developed to Prevent Dementia is Getting Support

    By Kathleen Berger, Executive Producer for Science and Technology

    A new vaccine technology at WashU is giving the idea of a dementia vaccine new potential. Both Alzheimer’s disease and frontotemporal dementia are devastating disorders following the buildup of misfolded proteins in the brain. The vaccines would generate anti-amyloid beta and anti-tau antibodies using a vaccine platform of peptide nanofibers.

    “Using nanomaterials as vaccine agents,” said Jai Rudra, PhD, associate professor of biomedical engineering at the McKelvey School of Engineering. “The platform itself has proven effective in multiple disease models. We tested vaccines against tuberculosis and herpes. We even did some cocaine-based vaccines to see if we can make antibodies against drugs of addiction. We’ve done HIV and a few other models.”

    The WashU research team is receiving a $2.9 million grant from the National Institute on Aging, part of the National Institutes of Health, to advance the nanofiber vaccine technology for dementia.

    “This is the first time we are attempting to address the question of whether we can get antibodies against neurodegenerative diseases, in particular, this time we are testing about Alzheimer’s to see if we can make antibodies against proteins that cause Alzheimer’s.

    Rudra partnered with Meredith Jackrel, PhD, an associate professor of chemistry in Arts & Sciences at WashU.

    “We study protein folding and misfolding, so we are really interested in understanding how proteins misfold at the biochemical and biophysical level, and then how that misfolding drives neurodegenerative disease,” Jackrel said.

    Having an effective and safe vaccine for Alzheimer’s disease is gaining importance. Recent Alzheimer’s drugs have not had the results the science community had hoped. So, Rudra and Jackrel are designing vaccines that will train a person’s own immune system to take out accumulations of amyloid beta and tau proteins.

    “The nanofiber serves as a carrier to take the protein in, stimulate the immune system and have the immune system make an antibody to that protein of interest that you are delivering with the nanofibers. So, the nanofibers are a delivery vehicle for any protein that you want to put into an animal to test whether the vaccine is efficacious or not.”

    “We can confirm if they are showing a proper effect in our animal system, that they don’t trigger Alzheimer’s proteins to aggregate in our cell lines,” said Jackrel.

    The key to the research team’s success is how the vaccine’s peptide nanofiber design does not cause the type of inflammation that can happen with other types of vaccines, as neuroinflammation is a concern.

    “In the many models that we tested, the nanofibers seem to generate an antibody response without the associated inflammation,” said Rudra.

    The nanofibers work better because amyloid beta and tau are presented on the surface of the nanofiber in such a way that the immune system will not generate as much inflammation in its wake.

    Jackrel and Rudra will work with WashU Medicine researchers to test their vaccines. Tim Miller, MD, PhD, the David Clayson Professor of Neurology, and Kathleen Schoch, an assistant professor of neurology, will assist by testing the vaccines on transgenic mice that develop disorders that mimic various dementias in the brain.

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