New Vaccine Formulation Shows Promise For Alzheimer’s Target
AC Immune CEO Andrea Pfeifer pictured above. Photo courtesy of AC Immune.
Switzerland-based AC Immune SAannounced positive interim results from its ongoing Phase Ib/IIa clinical trial of ACI-35.030 for Alzheimers disease. The vaccine showed a potent antigen-specific antibody response against phosphorylated tau in 100% of older patients with early Alzheimers.
AC Immune is working in collaboration withof Johnson & Johnson.
ACI-35.030 is a potent liposomal anti-pTau vaccine. It is engineered to elicit antibodies against phosphorylated pathological Tau protein, which is associated with Alzheimers disease. Two abnormal proteins in the brain are linked to Alzheimers, beta-amyloid and pTau. Generally, although not exclusively, beta-amyloid is seen earlier and pTau is seen later in the disease. ACI-35.030 is designed to decrease and help the clearance of aggregates of Tau.
The data demonstrated anti-tau IgG response preferentially targeted pTau in all patients, with 100% response after the first injection at both the lowest and second highest dosages. Very high anti-pTau IgG levels were observed after injection and the IgM response was also observed in all patients for both doses. The drug was safe and well tolerated with no clinically relevant safety issues. At this time, it plans to advance to the third and highest dosing levels, per study protocol.
The Importance Of Sex
When scientists studied the impact of vaccination on free forms of proteins and on already formed aggregates, they found that male and female mice did not react the same way. In male mice, the double vaccine has almost no effect on free amyloid proteins. For female mice, the reverse is true: the vaccine fighting both tau proteins and amyloid plaques significantly decreases the level of free amyloid proteins in the brain.
In the case of already formed amyloid plaques, there is less in males than in females after vaccination. If mice are not comparable to human beings, it still echoes the differences that we observe between men and women with Alzheimers disease. In France, 60% of Alzheimers patients are women and their cognitive impairments are different from those of men.
Heres How The Vaccine Works In Mice
The vaccine candidate was designed to target a specific type of protein known as pathological tau thats found in large amounts in the brains of people who have Alzheimers disease.
Although tau is present in everyones brains, the protein builds up in the brains of people with Alzheimers and is believed to cause cognitive decline.
Tau protein is present in normal and healthy brain cells, but in Alzheimers disease the protein accumulates abnormally in tangles that interfere with brain signaling and communication, explains Dr. Verna R. Porter, a neurologist and the director of the Alzheimers disease program at Providence Saint Johns Health Center.
The research team found that when the vaccine was administered to the mice, their bodies developed antibodies that removed the abnormal tau protein from the part of the brain associated with learning and memory.
The mice were then put to the test in several maze-like puzzle. The rodents that received the vaccine performed significantly better than those that did not get the vaccine.
The improvements lasted for months, the researchers reported.
Although the vaccine worked very well in the mice, again its important to remember that success in a mouse trial doesnt mean it will help humans.
In Alzheimers drug development, what we see in an animal is interesting, but we know that it cannot necessarily be reproduced in humans, Dr. Marwan Sabbagh, the director of Cleveland Clinic Lou Ruvo Center for Brain Health, said.
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Phase 1 Trial Will Test The Safety And Tolerability Of Vaccine
The trial contains 16 participants between 60 and 85 years of age with early, symptomatic AD. All the participants are in good general health with no disease expected to interfere with the study and have had an amyloid-positive PET scan.
Each of the subjects will get two doses of the nasal vaccine, with the second dose being delivered a week after the first. This trials primary objective is to find out if the vaccine is safe and well tolerated, and the impact of nasal Protollin on participants immune response, including its effects on white blood cells, will also be measured.
This vaccine goes to show the immune system is important for so many things outside of infection, such as neurological diseases, cancers, heart disease, and the list goes on, says Purvi Parikh, MD, a clinical assistant professor at NYU Grossman School of Medicine and immunologist at NYU Langone, both in New York City. Dr. Parikh is not involved in the clinical trial.
Its exciting that we can train our immune system with vaccines to fight these disease in an effective way, she says.
Low Side Effects In Mice With Mpl
Biologists speculate that the MPL acts at two levels. On the one hand, it would increase the number of blood stem cells, those that differentiate into microglial cells, thereby increasing the strength of the immune system in the brain. In addition, the molecule, by attaching itself to these cells, increases their appetite for senile plaques, which are better phagocytosed.
If from a biological point of view the progress is incontestable, it is necessary to take into account in addition the side effects when one intends to develop a vaccine. Contrary to the previous tests which had proved too heavy of consequences, theinflammation observed this time seems to be much more moderate. Enough to suppose that the treatment would be well supported by human subjects at equivalent doses.
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Third Doses For People With Weaker Immune Systems
People with weaker immune systems are being offered a third primary dose of the vaccine, which is separate from the booster vaccine.
For most people, having two doses of the coronavirus vaccine gives a very high level of protection. But for people who have weakened immune systems, the vaccine may not have worked as well. This means they could still be at risk of serious illness from coronavirus even after having both vaccinations.
To help build up enough protection against coronavirus, a third vaccine will be given for people whose immune systems do not work properly. It is recommended that this should be with the Pfizer or Moderna vaccines. This third dose is being offered to people with conditions like HIV and lymphomas, and people who take medicines that make their immune system weaker. This is in addition to the booster vaccine.
Having dementia or being older does not make a person eligible for a third primary dose, as the first two vaccines are likely to have worked well for these people. However, people over 50 and those living in care homes will be eligible for a third booster vaccination see below.
Full guidance from the JCVI about third doses for immunosuppressed people can be found on the government website.
Brigham And Women’s Hospital Launches Clinical Trial Of Nasal Vaccine For Alzheimer’s Disease
First human trial for intranasal vaccine for AD represents culmination of 20 years of research led at the Brigham
Brigham and Womens Hospital is set to begin a clinical trial that will test the safety and efficacy of a new vaccine delivered nasally intended to prevent and slow the progression of Alzheimers disease . The trial represents the culmination of nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the Brigham.
The launch of the first human trial of a nasal vaccine for Alzheimers is a remarkable milestone, said Weiner. Over the last two decades, weve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimers, and it could also be given early to help prevent Alzheimers in people at risk.
For 20 years, there has been growing evidence that the immune system plays a key role in eliminating beta amyloid. This vaccine harnesses a novel arm of the immune system to treat AD, said Tanuja Chitnis, MD, professor of Neurology at the Brigham and principal investigator of the trial. Research in this area has paved the way for us to pursue a whole new avenue for potentially treating not only AD, but also other neurodegenerative diseases.
Funding: This study is funded by I-Mab and NHWA.
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Good News Bad News From Alzheimer’s Vaccine Trial
An experimental Alzheimer’s vaccine appears to safely clear abnormal tau protein from the brain, but it’s not yet clear whether the shot will be able to save brain function.
In a Phase 2 clinical trial, the vaccine produced high levels of antibodies to target and attack free-floating tau proteins before they can form “tau tangles” that clog neurons and damage brain function. Tau tangles, along with plaques formed by the protein amyloid-beta, serve as one of the main hallmarks of Alzheimer’s.
“While amyloid influences speed of Alzheimer’s progression, there is strong evidence that tau pathology relates to the underlying cause of the disease,” said lead researcher Dr. Petr Novak, a senior clinical research scientist at AXON Neuroscience, the Slovakian pharmaceutical company developing the vaccine. “Brain atrophy and cognitive loss closely echo the deposition of pathological tau protein, as evidenced by recent tau PET studies.”
The vaccine also proved safe during the two-year trial, in which eleven doses were administered to randomly chosen patients with mild dementia. People who received the vaccine, known as AADvac1, experienced about the same numbers of side effects and adverse events as those who were given a placebo.
In that group, the vaccine slowed brain decline by around 30% in two different clinical and functional tests, Novak said.
In the current trial, a total of 196 patients were randomly chosen to receive either the vaccine or a placebo.
Explore further
A Preventive And Therapeutic Vaccine Against Alzheimers Disease
Article published on January 20, 2013 by Janlou Chaput
Are we finally getting closer to a vaccine against Alzheimers disease? Tested in mice, a molecule named MPL boosted the rodent immune system which destroyed 80% of senile plaques involved in dementia. All with very few side effects, a contrast strong with old attempts.
- To read, our dossier on Parkinson disease
Alzheimers disease is the worlds leading cause of dementia, and with the aging of the population, its incidence is estimated to increase sharply in the decades to come. However, there is no cure for the disease, or even preventive treatment.
It is not for lack of trying. At least a dozen vaccines have been tested over the past ten years without success. The last clinical test dated back to Swedish researchers from the Karolinska Institutet who published in The Lancet Neurology mixed results. If their molecule, CAD106, did stimulate the defenses against senile plaques, beta-amyloid agglomerates involved in neurodegeneration, Side effects for the patients were too important for the vast majority of them.
Research therefore continues to find a way to push the bodys defenses to destroy these plaques present between the neurones. The problem does not come from the synthesis of beta-amyloids, but rather from a deficit in their elimination. The cells of the brain immune system, the microgliagle cells, fail to get rid of them properly.
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Immunize Against Tau And
The vaccine recipe used by American researchers mixes two epitopes, specific for tau and -amyloid proteins, and a adjuvant polysaccharide. Its ability to induce a specific immune response has already been proven in 2016 by the same team. This time, they are testing their vaccine on mice genetically engineered to contract human Alzheimers disease and comparing its potential to vaccines directed against the tau or -amyloid protein alone.
As expected, the double vaccine induced a high concentration of antibodies specific to the tau and -amyloid proteins. As a result, these two proteins see their serum concentration and in brain extracts decrease, but an unexpected effect puts this result into perspective. Indeed, the immune response is not the same between male and female mice.
Trial Begins Of Nasal Vaccine For Alzheimer Disease
THURSDAY, Nov. 18, 2021 The first human clinical trial of a nasal vaccine to slow the progression of Alzheimer disease is set to begin after nearly 20 years of research.
This is a remarkable milestone, according to Howard Weiner, M.D., codirector of the Ann Romney Center for Neurologic Diseases at Brigham and Womens Hospital in Boston. Over the last two decades, weve amassed preclinical evidence suggesting the potential of this nasal vaccine for Alzheimer disease, Weiner said in a hospital news release. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimers, and it could also be given early to help prevent Alzheimers in people at risk.
The vaccine features an experimental agent called Protollin that stimulates the immune system. It is designed to prompt white blood cells in the lymph nodes on the sides and back of the neck to migrate to the brain and clear beta amyloid plaques.
The trial is funded by I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical, developers and makers of Protollin.
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Ongoing Clinical Immunotherapy Trials
It is a common belief that treatment is too late when these two features, amyloid plaques and neurofibrillary tangles, are already present. Intervention has to start early and from the current treatment options immunotherapy has the highest possibility to be effective. The medical term immunotherapy addresses the manipulation of the immune system by inducing, enhancing, or suppressing immune responses in vivo. Immunotherapy in AD covers two types of vaccination: active vaccination against Abeta42 in which patients receive injections of the antigen itself or passive vaccination in which patients receive injections of preformed antibodies against Abeta42. These antibodies are predicted to help with Abeta clearance via different pathways: antibody binding to Abeta in plasma might cause a gradient effect leading to Abeta removal from brain or the antibody binding might label Abeta in brain for the recognition by professional phagocytic cells in brain to remove the Abeta deposits. Preliminary data from our laboratory showed that antibodies from Abeta42 peptide immunizations can lead to high titers of Abeta42 antibodies in APP/PS1 double transgenic mice and that these antibodies directly bind to the plaques in brain and help to remove excess Abeta42 from brain .
Immunotherapy targeting the pathological forms of tau protein are in preclinical testing, analyzing this treatment in the respective mouse models in which they show positive results as well .
One More Step Towards A Vaccine Against Alzheimers
They are not the first researchers to come up with a vaccine concept against Alzheimers disease. This collaboration between the United Kingdom and Germany hopes to immunize against Alzheimers by injecting a free form of the amyloid protein, responsible for senile plaques. Promising results have just appeared in Molecular Psychiatry.
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A revolutionary implant to prevent Alzheimers diseaseAlzheimers disease progressively attacks neurons, first causing memory impairment until loss of autonomic functions and then death. Researchers at EPFL in Switzerland have developed a capsule that could protect neurons and stop disease. Here is how it works presented in video.
The idea has been gaining ground in the scientific community in recent years: to develop a preventive treatment against Alzheimers disease. Target the tau protein and -amyloid at the same time or strengthen the immune defenses of the brain, scientists have tested several approaches that have delivered interesting fundamental results, but which have not yet translated into a significant advance in the management of Alzheimers.
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How Can I Get My First Or Second Coronavirus Vaccines
The vaccines have already been offered to people in huge numbers. Some people will get a letter inviting them to book an appointment.
If you are not currently registered with a GP, you should register now to get a vaccine.
If you have not had your first or second coronavirus vaccines, you can book an appointment on the NHS coronavirus vaccination website. You can also call 119 for free, between 7am and 11pm seven days a week.
All vaccines are free and you should not be asked for any payment. People will not be given a choice of which vaccine they are offered.
The guidance from the government’s Joint Committee for Vaccination and Immunisation sets out the priority groups for vaccination.
A Vaccine For Alzheimers Disease An Interview With Ac Immunes Prof Andrea Pfeifer
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The fourth clinical-stage tau program is a diagnostic candidate designed to improve assessment of tau-pathology in AD and diagnosis of other tau-related diseases such as progressive supranuclear palsy :
- PI-2620 our tau-PET tracer this asset has the potential to work as a critical tool in the further development of anti-tau approaches by facilitating the design of clinical trials that treat earlier and target more homogeneous populations.
Andrea Pfeifer was speaking to Ruairi J Mackenzie, Science Writer for Technology Networks
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Boston Hospital Launches First Human Trial Of Nasal Vaccine For Alzheimers Disease
Researchers hope vaccine could offer a safe and effective way to prevent or slow down progression of AD.
Brigham and Womens Hospital in Boston is set to begin a clinical trial that will test the safety and efficacy of a new vaccine delivered nasally that has been developed to prevent and slow the progression of Alzheimers disease .
The launch is a remarkable milestone, said Howard L. Weiner, MD, codirector of the Ann Romney Center for Neurologic Diseases at the Brigham, in a press release. Over the last two decades, weve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimers, and it could also be given early to help prevent Alzheimers in people at risk, he said.
An estimated 55 million people live with dementia, which is a general term for impaired ability to remember, think or make decisions beyond what might be expected from the usual consequences of growing old, according to the World Health Organization . Alzheimers disease is the most common form of dementia, and may account for 60 to 70 percent of cases.