Inside the race to cure Alzheimer’s with a vaccine – as six experimental shots enter trials

They’ve cured countless childhood diseases and dragged us out of the Covid pandemic, and now, vaccines could be set to treat and prevent Alzheimer’s disease.

After decades of failed trials, ineffective drugs and billions of dollars spent, a new frontier of shots offer a glimmer of hope for current and future sufferers of the cruel condition that affects 5.8million Americans.

While there have been recent breakthroughs with the approval of IV treatment Leqembi and the soon-to-be-approved drug donanemab, these require hours-long infusions multiple times a month and can cost up to $26,000 per year. And effects are marginal at best – giving patients a few extra months of health.

Importantly, some doctors have raised concern about the safety of these drugs, amid reports of catastrophic brain bleeds – and even deaths – in patients on the clinical trials. 

Over the last decade, researchers have focused their attention on vaccines, which are cheaper, more accessible and have more accommodating administration schedules.  

There are currently at least six clinical trials either completed or in progress testing the safety and efficacy of vaccines to treat and prevent Alzheimer’s disease that DailyMail.com has explained below, including how researchers hope they work and when they could possibly become available. 

There are at least six Alzheimer’s vaccines currently in the works, and patients can expect to access them in a few years

While two vaccines have shown promising results and earned them FDA fast track consideration for approval, patients will likely still have to wait a few years before they can access them. 

As the aging population of the US continues to grow, so will the rates of dementia. Currently, an estimated 5.8million Americans have Alzheimer’s disease – the most common cause of dementia – the vast majority of whom are aged over 65. By 2050, this number is projected to rise to nearly 13 million.

While the main cause of Alzheimer’s disease is still debated, scientists believe the damage is likely to be the result of abnormal build-up of proteins – amyloid and tau – in and around brain cells. 

For decades, Alzheimer’s researchers have focused on developing drugs that target clumps of amyloids – a hallmark sign of AD. However, they have recently turned their focus to how tau proteins play a role in cognitive decline.

Unlike amyloid, which accumulates widely across the brain and sometimes in people with no dementia symptoms at all, autopsies of AD patients reveal tau is concentrated precisely where brain atrophy is most severe.

Accumulation of tau is also seen in specific locations that may explain the difference in patient’s symptoms, such as language-related areas of the brain or memory-related areas.

AD treatments have aimed to slow the build-up of these proteins, or destroy the deposits that have already formed.  

Vaccines for Alzheimer’s disease have been in development for more than two decades, but the first trial was terminated when six percent of the volunteers developed a type of life-threatening brain swelling called meningoencephalitis.

Research pivoted, with treatments instead focused on infusing man-made antibodies into patients via a drip in the arm, rather than vaccines. 

Trials of these treatments, such as Leqembi and donanemab proved removing the amyloid plaque clusters was key to fighting Alzheimer’s in early stages. 

The above graph shows the estimated projection of Alzheimer’s disease patients in the US through 2060.

Following that discovery, many of today’s vaccines – being studied in multiple doses and given at varying intervals throughout the year – are designed to provoke the body’s immune system into producing antibodies that fight amyloids and tau. 

Most of the newer vaccines use immunotherapy – a treatment that uses a person’s own immune system to fight a disease.

Specifically, they increase the activity of B cells – immune cells that are primed to hunt and fight specific intruders.

Scientists are hoping the vaccines will successfully recruit the body’s own ‘fighter’ cells to track down and destroy amyloid plaques and tau tangles.

Some of the shots are up to 98 percent effective at triggering this ‘fighter’ immune response, according to the small trials that have been conducted so far.

Dr Reisa Sperling, an Alzheimer’s researcher at Mass General Brigham in Boston, told Reuters that developing vaccines is ‘where we need to go’ when it comes to preventing the disease.

And a vaccine given a few times a year could be a welcome alternative to Leqembi’s expensive twice-monthly infusions.

Leqembi is estimated to cost $26,500 per year.  

Similarly, donanemab is administered to patients via once-a-month intravenous injections for up to 18 months.

A cost for the drug is yet to be revealed, but researchers have suggested it will be priced at $1,600 per dose or $20,000 annually.

Dr Walter Koroshetz, director of the neurological disorders division of the National Institutes of Health, told Reuters that vaccines, ‘could be worldwide, and not that expensive’.

Here, DailyMail.com unveils the fascinating details of six promising anti-dementia shots – including how soon they could be available.

Vaxxinity: ‘Most advanced’ immunotherapy

When you hear immunotherapy, you normally think of cancer, but Vaxxinity’s vaccine, dubbed UB-311, is an active immunotherapy vaccine that targets the toxic amyloid buildup in the brain associated with Alzheimer’s. 

Among the several vaccines in production, Vaxxinity’s may be the furthest along, having completed its Phase 2 trial. 

However, the company has been unable to find an international partner to help fund a larger, confirmatory trial.

In May 2022, Vaxxinity received fast track designation for the vaccine, which it hails as the ‘most advanced’ immunotherapy. 

With an FDA fast track designation, the agency expedites its review process in order to get breakthrough drugs to market quicker. 

For drugs to be granted this status, they must show ‘superior effectiveness,’ avoid side effects of available therapies, improve diagnosis of a serious condition and be able to address an emerging public health need. 

Publishing results from its trial in August 2023, Vaxxinity said the vaccine proved to be safe and tolerable among the 43 participants who had mild Alzheimer’s disease. 

Data showed there was a 97 percent antibody response and scientists saw a trend of slowing cognitive decline in people who received the vaccine compared to those who received placebo. 

Side effects of the vaccine were mild and included irritation at the injection site, injection-site pain and swelling. Six patients did experience slight brain bleeding, which is a side effect common with infusion treatments, but the company still reported the safety of the vaccine was comparable to that of the placebo. 

In the 78-week Phase 2 trial, UB-311 ‘elicited a robust, rapid… antibody response. UB-311 was generally well-tolerated.’ 

There were three groups of participants. Group 1 received seven doses of the vaccine over the 78-week period. Group 2 received five doses of UB-311 and two doses of placebo and group 3 received seven doses of placebo. 

Dr Jeffrey Cummings, who co-authored the paper announcing the trial results, said in an August 2023 press release: ‘The UB-311 Phase 2a program accomplished its goals of establishing safety and tolerability, while generating high levels of anti-amyloid antibodies.

‘Vaccine approaches such as UB-311 represent important ways forward in advancing treatment and prevention of Alzheimer’s disease and offer the potential to transform the treatment landscape by providing participants with an accessible therapeutic option.’

Axon Neuroscience: Positive trial results and seeking a partner for future studies

Like UB-311, Axon Neuroscience’s immunotherapy active vaccine has finished its Phase 2 trial with positive results  but has been unable to find a partner to help with clinical development.

The trial was a two-year study to assess the safety and efficacy of the vaccine, which, dependent on time of approval, could be the first tau-targeted vaccine offered to patients. While research into vaccines against amyloids have been around for decades, vaccines targeting tau proteins are fairly new. 

Results showed the vaccine demonstrated excellent safety and ‘robust’ antibody production in people with mild AD. The company reported there was no difference in adverse events between the group that received placebo and the group that received the vaccine. 

In the trial of 196 people, the treatment was shown to be highly effective in inducing a robust immune response, with 98 percent of patients generating antibodies against tau. 

The vaccine ‘showed a strong efficacy signal, demonstrated by significant slowing of clinical and functional decline.’

The trial found the vaccine slowed the progression of the neurodegenerative process seen in AD to that more typically seen in healthy people.  

Michal Fresser, CEO of Axon Neuroscience, said in a September 2019 press release announcing the results: ‘Today’s results mark an important milestone for Axon, and for the entire population of the world that suffers from this devastating disease. 

‘Our vaccine is the first to solely target pathological tau proteins, which drive the cognitive decline and memory loss seen in Alzheimer’s. These results, which strongly reveal a disease-modifying effect on the disease, underpin our confidence to take the next steps in bringing a life-changing treatment to patients as soon as possible.’

Janssen/AC Immune: Could treat and prevent Alzheimer’s 

A vaccine from AC Immune and the Janssen Pharmaceuticals arm of Johnson & Johnson also seeks to target tau.

The anti-pTau vaccine is aimed to reduce the spread of tau and its tangles in the brains of people with AD. A Phase 1/2 clinical trial with 57 patients suffering from early AD was only just completed in September but preliminary data shows the vaccine ‘rapidly leads to the strong and durable induction of antibodies’ against Tau and is generally well tolerated. 

The vaccine was trialed in three different doses, with multiple shots administered at predefined times over a 48-week period.  

The average age of the trial participant was 65 years old, which indicates this vaccine could become both a treatment and preventative measure for Alzheimer’s disease.  

The ‘excellent performance’ of the vaccine ‘potentially opens promising avenues for Alzheimer’s disease treatment and prevention, which could offer an important societal impact.’ 

The company said the vaccine could be the first tau-targeted drug, dependent on time of approval.

AC Immune: Received FDA Fast Track designation

A second AC Immune vaccine is an anti-amyloid vaccine that received FDA fast track designation in June 2023. The company currently has an ongoing Phase 1/2 trial that includes 140 people.

The active immunotherapy vaccine targets anti-amyloid beta and aims to elicit the production of antibodies. It is currently being trialed at six doses in people with mild AD.

In January, the company said the drug produced an immune response and there were no safety concerns, demonstrating the vaccine was ‘generally well tolerated,’ and participants in the trial produced an antibody response as soon as two weeks after their second injection.

The study is now testing a higher dose of the vaccine and the trial will run through June 2026. The company does not have published data yet.

The vaccine is aimed to ‘ultimately deliver significant benefits to patients, their caregivers, and healthcare systems in terms of potential safety and tolerability, low frequency dosing, low overall costs and durable responses.’ 

AC Immune says the vaccine has the potential to block plaque formation and increase plaque clearance, possibly reducing or preventing Alzheimer’s progression.

Alzinova: Produces antibodies against amyloid plaques in brain

A trial for a vaccine in development by Alzinova is ongoing through the end of next year, but preliminary data shows it also produces antibodies against amyloid plaque in the brain. 

The vaccine is currently being tested in a 20-week Phase 1 study in 27 people with early AD. The company said its shot, ALZ-101, neutralizes the toxic buildup of amyloid-beta, which is central to the onset and development of Alzheimer’s. 

The study has three groups of participants: One receives four doses of placebo, one receives four low doses of the vaccine and one receives four high doses of the vaccine, all given over 16 weeks.

The vaccine seems to be generally well tolerated, but no data in human trials has been published yet. The trial began in September 2021 and is estimated to be complete December 2024, but the company could see preliminary data before the end of 2023. 

In mice, rabbits and non-human primates, the vaccine did generate an immune response and was shown to be clinically well tolerated.

National Institutes of Aging: Entered human trials in February

A vaccine funded by the National Institutes of Aging, AV-1959D, entered human trials in February for people with early AD. Its Phase 1 trial includes 48 participants and is estimated to conclude February 2026. 

The trial will test the safety and tolerability of the vaccine at three doses compared to volunteers receiving a placebo treatment. 

Because the trial has only just begun, there is no information on the vaccine’s safety, tolerability or efficacy in humans. 

However, the DNA-based vaccine showed in animal studies it was safe and effective at preventing amyloid accumulation and brain cell death associated with AD.