Study co-author Prof. Nikolai Petrovsky, of Flinders University School of Medicine in Australia, and colleagues reveal how a vaccine combination generates antibodies that target beta-amyloid and tau proteins in the brain – both of which are considered hallmarks of Alzheimer’s disease.
Beta-amyloid is known to accumulate in the brains of people with Alzheimer’s, forming plaques, while the tau protein forms tangles. Plaques and tangles are believed to disrupt signaling between nerve cells and contribute to nerve cell death.
“[The proteins are] a bit like the car in your driveway,” Prof. Petrovsky explained to ABC Adelaide. “You need to remove them from the brain otherwise if you left broken down cars in your driveway eventually you couldn’t get out.”
“Essentially that’s what happens in people who get Alzheimer’s or dementia is they have lots of these broken down proteins in the brain.”
Reporting in the journal Scientific Reports, the team describes how the vaccine formulation has proven safe and effective in mouse models of Alzheimer’s, and it has also successfully targeted beta-amyloid and tau proteins in human brain tissue.
Vaccine combo boosts antibody response to Alzheimer’s proteins
Researchers have spent decades searching for ways to prevent and treat Alzheimer’s, but success has been limited.
Between 2002-2012, 413 clinical trials were conducted worldwide that assessed the safety and efficacy of 244 compounds against Alzheimer’s. Only one new drug came out of these trials – representing a 0.4 percent success rate – and this drug only induces short-term relief of Alzheimer’s symptoms.
As a result of such poor outcomes from clinical trials to date, the National Institutes of Health (NIH) increased their funding for Alzheimer’s research by $350 million, bringing the total funding for research in the U.S. to $1.3 billion this year.
According to Prof. Petrovsky and colleagues, such funding has led to the development of their “exceptional” vaccine, which they say is comprised of a MultiTEP vaccine platform and Advax.
The team explains that the MultiTEP approach produces high antibody responses to beta-amyloid and tau proteins either independently or combined, while Advax is an adjuvant vaccine that further boosts the antibody response.
In their study, the researchers found that the formulation was effective and well-tolerated in Alzheimer’s mouse models, with no reports of adverse reactions. The vaccine was also able to target the proteins in brain tissue from patients with Alzheimer’s.
“This study suggests that we can immunize patients at the early stages of AD [Alzheimer’s disease], or even healthy people at risk for AD, using our anti-amyloid-beta vaccine, and, if the disease progresses, then vaccinate with another anti-tau vaccine to increase effectiveness.”
Study co-author Prof. Michael Agadjanyan, Institute for Molecular Medicine, California
According to the Alzheimer’s Association, around 5.4 million people in the U.S. are living with Alzheimer’s, and this number is expected to almost triple by 2050 unless new, effective treatment strategies are uncovered.
The researchers say they will be working with four companies to assess the non-clinical safety and toxicology of the vaccine, which is required under the U.S. Food and Drug Administration’s (FDA) Investigational New Drug program.
If the vaccine continues to show success in these preclinical trials, the researchers say they could be testing the vaccine in individuals at high risk for Alzheimer’s or those in the early stages of the disease within the next 3-5 years.