Experimental Alzheimer’s Vaccine Shows Promise – Neuroscience News
2025-04-24T12:59:35Z
Researchers have developed a tau-targeting vaccine that could help prevent the progression of Alzheimer’s disease by generating a strong immune response against abnormal tau proteins.
Summary: Researchers have developed a tau-targeting vaccine that could help prevent the progression of Alzheimer’s disease by generating a strong immune response against abnormal tau proteins. The vaccine showed effectiveness in mice and non-human primates, prompting researchers to pursue human clinical trials.
It targets a specific region of the tau protein, pT181, linked to Alzheimer’s-related brain damage and cognitive decline. If successful in humans, this approach could complement or even surpass current therapies that only modestly impact disease progression by targeting amyloid beta.
Key Facts:
Tau-Targeting Vaccine: Generates antibodies against pT181, a hallmark of Alzheimer’s pathology.
Generates antibodies against pT181, a hallmark of Alzheimer’s pathology. Strong Immune Response: Proven effective in mice and macaques, with long-lasting immunity.
Proven effective in mice and macaques, with long-lasting immunity. Clinical Trials Ahead: Researchers are preparing for Phase 1 human trials pending funding.
Source: University of New Mexico
University of New Mexico Health Sciences researchers hope to launch human clinical trials in their quest for a vaccine to prevent the buildup of pathological tau – a protein in the brain associated with Alzheimer’s dementia.
In a new paper published in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, a team led by Kiran Bhaskar, PhD, professor in the Department of Molecular Genetics & Microbiology in the UNM School of Medicine, found that the experimental vaccine generated a robust immune response in both mice and non-human primates, building on earlier research.
The vaccine elicited a strong immune response in two other strains of mice bred to develop tau-related disease – one of which had a human tau gene inserted in its genome. Credit: Neuroscience News
“Because we’ve shown efficacy in the non-human primate, I think that is suggesting to us it’s much closer to a clinical trial,” Bhaskar said, adding that he and his colleagues are seeking funding from venture capitalists and the Alzheimer’s Association to launch a Phase 1 trial in humans.
Tau is a naturally occurring protein that helps stabilize neurons, but when it undergoes a process called phosphorylation, it deforms and is ejected from neurons into the extracellular space, creating the tangles that are characteristic of Alzheimer’s and other neurodegenerative diseases.
There are several new FDA-approved treatments for drugs that reduce levels of amyloid beta, another protein implicated in Alzheimer’s pathology, but they have only a modest effect on the progression of the disease, leading many to wonder whether targeting tau might be a better bet.
The active immunotherapy developed at UNM generates antibodies that bind to pT181, a region of the altered tau protein that has been identified as an Alzheimer’s biomarker.
In a 2019 paper published in NPJ Vaccines, Bhaskar and his colleagues reported that when the vaccine was given to mice bred to express pathological tau they generated antibodies, reduced the extent of the tangles in key brain structures and improved their performance on tests to gauge their cognitive disability.
The new paper expands on those findings. The vaccine elicited a strong immune response in two other strains of mice bred to develop tau-related disease – one of which had a human tau gene inserted in its genome.
In a collaboration with the University of California, Davis, and the California National Primate Research Center the vaccine was also administered to macaques, primates whose immune systems and brains are closer to humans. They also showed a strong and durable immune response.
The researchers also tested antibodies in the serum from the immunized monkeys on samples of blood plasma drawn from people with mild cognitive impairment, often a precursor to full-blown Alzheimer’s dementia, as well as the sera in brain tissue from people who had died from Alzheimer’s, and found that they bound to the human version of the tau protein.
The vaccine was developed using a virus-like particle (VLP) platform developed by Bryce Chackerian and David Peabody, Bhaskar’s colleagues in Molecular Genetics & Microbiology.
VLPs are essentially viruses whose DNA has been removed, rendering them harmless. Snippets of proteins – in this case pT181 – can be attached to their surface, rendering them visible to immune cells on the lookout for invaders.
VLP-based vaccines have been shown to create durable immunity, with one primary inoculation and two booster shots, Bhaskar said.
They don’t require adjuvants – substances (such as aluminum) administered with a vaccine to enhance the immune response. And, they have been shown to be safe in humans.
Nicole Maphis, PhD, a postdoctoral researcher in the UNM Department of Neurosciences, was the first author on both of the vaccine papers. She said the collaboration with UC Davis was critical for validating the vaccine’s efficacy.
“This was important because it extends our work in an animal model that is more similar to humans,” she said.
“Mice don’t have a human immune response, but these non-human primates, their immune response is much more similar to humans.”
About this Alzheimer’s disease research news
Author: Chris Ramirez
Source: University of New Mexico
Contact: Chris Ramirez – University of New Mexico
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques” by Kiran Bhaskar et al. Alzheimer’s & Dementia
Abstract
Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques
INTRODUCTION
Pathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer’s disease (AD), and correlates with cognitive decline. A rapid surge in tau-targeted approaches via anti-sense oligonucleotides, active/passive immunotherapies suggests that targeting p-Tau is a viable strategy against tauopathies.
METHOD
We describe a multi-species validation of our previously described Qß virus-like particle (VLP)–based vaccine technology targeting phosphorylated tau on threonine 181 (pT181-Qß).
RESULTS
Two vaccine doses of pT181-Qß, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes/neuroinflammation, and improved recognition memory and motor function without inducing adverse T-cell activation. Anti-pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable.
DISCUSSION
Our results suggest the translational utility of pT181-Qß against tauopathies.
Auto-posted from news source
About The Author
