Summary: Researchers have created a tau-targeting vaccine that could help stop Alzheimer’s disease from progressing by triggering a robust immune response to excessive beta proteins. Scientists were inspired to conduct human clinical trials because the vaccine demonstrated efficacy in both non-human and mouse monkeys.
It targets a particular area of the beta proteins, pT181, which is linked to cognitive decline and Alzheimer ‘s-related head injury. By targeting amyloid alpha, this approach may enhance or even beat existing treatments that only slightly affect disease progression in humans.
Important Information:
- The pT181 antibody is produced by the Tau-Targeting Vaccine, a essence of Alzheimer’s disease.
- Strong Immune Response: Has demonstrated long-lasting resistance in mice and lemurs.
- Prior to Phase 1 human tests: Experts are getting ready for Phase 1 clinical trials.
University of New Mexico
In their search for a vaccine to stop the development of compulsive beta, a protein that is thought to be associated with Alzheimer’s memory, researchers at the University of New Mexico Health Sciences hope to conduct human clinical trials.
A team led by Kiran Bhaskar, PhD, teacher in the UNM School of Medicine’s Department of Molecular Genetics &, Microbiology, discovered in a fresh paper published in Alzheimer’s and memory: The Journal of the Alzheimer’s Association that the empirical vaccine induced a strong immune response in both animals and non-human monkeys, building on earlier studies.
According to Bhaskar, “we’ve shown efficacy in the non-human ape, which suggests that a medical test is much closer to it,” adding that he and his associates are looking for funding from venture businessmen and the Alzheimer’s Association to build a Phase 1 study in people.
Tau is a naturally occurring protein that aids in neurodegenerative stability, but when it goes through a process known as phosphorylation, it deforms and is ejected from neurons into the extracellular space, resulting in the tangles that are characterized by Alzheimer’s and other neurodegenerative diseases.
Many people are now asking whether targeting tau might be a better choice because there are several new FDA-approved treatments for drugs that lower levels of another protein implicated in Alzheimer’s pathology.
The active immunotherapy at UNM produces antibodies that bind to pT181, a region of the altered tau protein that has been linked to Alzheimer’s disease.
In a 2019 paper published in , NPJ Vaccines, Bhaskar and his colleagues reported that when the vaccine was administered to mice bred to express pathological tau, they produced antibodies, reduced the size of the tangles in crucial brain structures, and improved their cognitive capacity.
Those findings are expanded upon in the new paper. Two other mice bred to develop tau-related disease, one of which had a human tau gene inserted into its genome, also exhibited a strong immune response as a result of the vaccine.
The vaccine was also given to macaques, primates whose immune systems and brains are more similar to humans, in a collaboration with the University of California, Davis and the California National Primate Research Center. A robust and long-lasting immune response was also observed.
The researchers also examined the antibodies in the immunized monkeys ‘ serum on blood samples from people who had died from Alzheimer’s disease, which are frequently precursors to full-blown Alzheimer’s dementia, as well as the sera in brain tissue from people who had previously had full-blown Alzheimer’s disease, and found that they bound to the human version of the tau protein.
The vaccine was created using a virus-like particle (VLP ) platform created by Bryce Chackerian and David Peabody, Bhaskar’s collaborators in Molecular Genetics & Microbiology.
VLPs are essentially viruses that have their DNA removed, making them harmless. In this case, pT181 can be attached to their surface, making them visible to immune cells on the lookout for invaders.
One primary inoculation and two booster shots have been shown to produce long-lasting immunity, according to Bhaskar.
They don’t need adjuvants, which are substances ( such as aluminum ) that are given together with a vaccine to boost the immune response. Additionally, they have been demonstrated to be safe in people.
The first author of both vaccine papers was PhD researcher Nicole Maphis, PhD, in the UNM Department of Neurosciences. She claimed that UC Davis ‘ collaboration was crucial to proving the vaccine’s efficacy.
This was crucial because it extended our research in a more human-like animal model, she said.
Although mammals don’t have a human immune response, these non-human primates ‘ immune response is much more similar to that of humans.
About this research on Alzheimer’s disease
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: Free of charge.
By Kiran Bhaskar and colleagues,” Targeting of phosphorylated tau at threonine 181 by a Q virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques.” Dementia and Alzheimer’s
Abstract
In mice and rhesus macaques, the vaccine that targets the phosphorylated tau at threonine 181 is safe, highly immunogenic, and lowers the severity of the disease.
INTRODUCTION
Alzheimer’s disease ( AD ) is a number of tauopathies that are linked to pathological accumulation of tau (pTau ), and their cognitive decline is correlated with this. A recent rise in tau-targeted therapies using active/passive immunotherapies and anti-sense oligonucleotides suggests that targeting p-Tau is a viable treatment for tauopathies.
METHOD
We present a multi-species validation of our previously described Qß virus-like particle (VLP)-based vaccine technology that targets phosphorylated tau on threonine 181 (pT181-Qß ).
RESULTS
In two different mouse models of tauopathy ( PS19 and hTau ) and rhesus macaques, two vaccine doses of pT181-Qß, without any adjuvants, elicited robust antibody responses. In mouse models, vaccination improved recognition memory, motor function, and reduced AT180+ hyperphosphorylation, Sarkosyl insoluble, and Gallyas silver positive tau, all without triggering adverse T-cell activation. Anti-pT181 antibodies are bioavailable in the central nervous system and are reactive to pTau in human AD brains and pT181+ tau in human brain lysates.
DISCUSSION
Our findings support the translational efficacy of pT181-Qß in the treatment of tauopathies.
