Scientists reprogram brain immune cells to fight Alzheimer’s

Researchers in Spain and Switzerland have identified an experimental molecule that may help restore the brain's natural defenses against Alzheimer's disease. The compound, known as OLE, appears to "reprogram" microglia, the brain's immune cells, allowing them to regain some of their protective abilities.

The research was led by José Vicente Sánchez Mut of the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH), together with Johannes Gräff of the École Polytechnique Fédérale de Lausanne (EPFL). Their findings were published in the journal Cell Death and Disease.

According to the study, OLE helps microglia surround and contain beta-amyloid plaques, reducing both their size and their harmful effects. In animal studies, the treatment also led to better performance on memory tests.

How OLE Targets Alzheimer's Disease

One of the hallmarks of Alzheimer's disease is the buildup of beta-amyloid plaques in the brain. At the same time, microglia, which normally help remove these toxic deposits, gradually become less effective. As their protective functions decline, they can contribute to damage in brain cells.

The researchers found that OLE, a molecule derived from the PM20D1 gene, can shift microglia back into a more protective state. After treatment, the cells moved toward beta-amyloid plaques and surrounded them, creating a barrier that limited contact between the plaques and nearby neurons. This reduced the plaques' toxic impact on brain tissue.

"One of the most significant findings is that we have identified a molecule capable of restoring microglia's protective function," explains Sánchez Mut. "In Alzheimer's disease, these cells become progressively impaired. Our results suggest that this process can be reversed, pointing to new therapeutic and research avenues to counteract the disease," adds the researcher, who leads the Functional Epi-Genomics of Aging and Alzheimer's Disease laboratory at the IN CSIC-UMH.

Testing OLE in Worms and Mice

To evaluate the effects of OLE, the researchers used several experimental models.

The first involved genetically modified worms (C. elegans) that produce beta-amyloid. Because these worms develop disease-related damage quickly, they provide a useful way to study toxicity. Treatment with OLE reduced the buildup of protein aggregates and improved the animals' movement, indicating a protective effect.

The team then tested the compound in mouse models of Alzheimer's disease. Mice received OLE for three months, after which researchers examined both memory and brain changes. The treated animals performed better on memory tests and showed fewer beta-amyloid plaques than untreated mice.

Microglia Show the Strongest Response

To better understand how OLE works, the researchers examined the activity of thousands of individual cells in the brain. Their analysis revealed that microglia were the cells most strongly affected by the treatment.

Following exposure to OLE, microglia activated pathways involved in clearing beta-amyloid and regained their ability to move toward plaques and contain them.

"Single-cell analysis allowed us to determine that microglia were the cells that responded most strongly to the treatment," says Victoria Pozzi, first author of the study. "From there, we observed that the compound helped these cells move toward beta-amyloid plaques and better contain the damage associated with the disease," adds the researcher.

Additional experiments in cell cultures produced similar results. Microglia treated with OLE were more effective at moving toward beta-amyloid deposits and helping remove them. In separate neuronal cultures exposed to conditions resembling those seen in Alzheimer's disease, OLE improved cell survival, suggesting the compound may also directly protect neurons.

Potential for Future Alzheimer's Therapies

The findings are covered by two European patents, including one owned by the CSIC. The researchers say this strengthens the translational potential of the work and supports future efforts to develop therapeutic applications based on the discovery.

The study received funding from the Dementia Research Switzerland -- Synapsis Foundation (Switzerland), the Pasqual Maragall Researchers Programme (PMRP) of the Pasqual Maragall Foundation, the Spanish Ministry of Science, Innovation and Universities, the Severo Ochoa Centres of Excellence programme of the State Research Agency (AEI), the Prometeo program of the Generalitat Valenciana, the European Regional Development Fund (ERDF), and the CSIC Interdisciplinary Thematic Platform PTI+ NEURO-AGING. Additional support came from the Swiss National Science Foundation, the École Polytechnique Fédérale de Lausanne (EPFL), the European Research Council (ERC), the National Research Foundation of Korea (NRF), and the European Social Fund (ESF+).

Journal Reference:

1. Victoria Pozzi-Ruiz, Aida Giner de Gracia, Liliane Glauser, Mario Romani, Fatima Gunter-Rahman, Alejandro González-Ramón, Mahmood Haj-Yahya, Rajasekhar Kolla, Allison M. Burns, Hilal A. Lashuel, Johan Auwerx, Johannes Gräff, Jose V. Sanchez-Mut. The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease. Cell Death, 2026; 17 (1) DOI: 10.1038/s41419-026-08791-1

Courtesy:

Universidad Miguel Hernandez de Elche. "Scientists reprogram brain immune cells to fight Alzheimer’s." ScienceDaily. ScienceDaily, 19 June 2026. <www.sciencedaily.com/releases/2026/06/260619020506.htm>. 

 

AI-designed universal coronavirus vaccine passes first human trial

A new type of universal coronavirus vaccine has passed its first human clinical trial, marking an important step toward broader protection against future virus outbreaks.

Developed by researchers at the University of Cambridge and the university spinout company DIOSynVax (DVX) Ltd, the experimental vaccine was found to be safe and caused no significant side effects in a study involving 39 healthy volunteers.

Unlike conventional vaccines that target specific virus strains, this vaccine was designed to protect against multiple members of the Sarbeco coronavirus family. This group includes SARS-CoV-2, the virus responsible for the COVID-19 pandemic, as well as SARS and several related bat coronaviruses that could potentially spill over into humans in the future.

The trial showed that the vaccine stimulated immune responses not only against SARS-CoV-2 and SARS, but also against related bat viruses that have not yet infected humans.

The findings were published in the Journal of Infection.

AI Designed Vaccine Technology

The study also marked another milestone. It was the first time a vaccine whose active ingredient was created entirely through computer simulations was tested in people.

Researchers used artificial intelligence and machine learning to design what they call a "super-antigen." The antigen is the component of a vaccine that trains the immune system to recognize and fight infection.

Rather than focusing on a single virus strain, the AI system analyzed genetic information from Sarbeco coronaviruses collected through surveillance programs worldwide. Using this information, it identified features shared across the entire virus group and combined them into a single vaccine antigen.

The goal is to create protection not only against known viruses, but also against future strains that have not yet emerged.

"This trial proves the safety of an entirely new way of designing vaccines. The technology uses an AI-designed 'super-antigen' to provide lasting protection against a broad range of viruses -- for example the Ebola group, or Sarbeco coronavirus group -- even as they mutate."

Researchers believe the same strategy could eventually be applied to other virus families, including Ebola viruses and influenza viruses.

Moving Beyond Constant Vaccine Updates

Many current vaccines, including seasonal flu shots and updated COVID-19 vaccines, are designed around virus strains already circulating in people. Because viruses evolve continuously, vaccines often need regular reformulation and annual updates.

Professor Jonathan Heeney from the Lab of Viral Zoonotics in the University of Cambridge's Department of Veterinary Medicine, who led the scientific research, said the new approach could help solve that problem.

"We've converted vaccine development from being reactive to being future proof. Our vaccines will continue to provide protection against viruses even as they mutate into new strains," said Heeney.

He added: "We've overcome the problem of traditional vaccines, which have limited protection. It means we can escape the constant cycle of chasing the virus variants circulating in humans and updating the vaccines to try to catch up, like a dog chasing its tail."

By targeting features shared across an entire virus family, researchers hope the vaccine will remain effective even as new variants appear.

Human Clinical Trial Results

Volunteers between the ages of 18 and 50 received the vaccine at National Institute for Health and Care Research (NIHR) Clinical Research Facilities in Southampton and Cambridge.

The study was sponsored by University Hospital Southampton NHS Foundation Trust (UHSFT).

The vaccine's super-antigen can be used with several different vaccine delivery platforms. In this trial, researchers delivered it as a DNA vaccine using a micro fluid jet system.

Because the method does not require a needle, it could offer an alternative for people who are uncomfortable with injections. Researchers also believe it may make large scale vaccination campaigns easier and faster, particularly in settings where traditional injections are more difficult to administer.

Before human testing began, animal studies showed the vaccine could generate strong immune responses against multiple coronaviruses.

The vaccine still requires additional testing before it could become available for public use. A larger Phase 2 study is planned to evaluate immune responses in a broader and more diverse group of participants and to confirm the vaccine's ability to generate strong, wide ranging protection.

Preparing for Future Pandemic Threats

Scientists say the need for broader vaccine protection remains urgent because many potentially dangerous viruses continue to circulate in animals around the world.

"Viruses like Influenza, Coronaviruses and the Ebola group are evolving continuously and by the time vaccines are rolled out, they may be poorly matched -- the current "reactive" vaccine system struggles to keep pace," said Professor Saul Faust from the University of Southampton, the trial's chief investigator.

He added: "This new class of universal vaccines are future-proofed. They not only protect against many variants simultaneously, but potentially against related viruses that haven't yet emerged and spilt over to humans.

"If we can develop and clinically advance this new class of vaccines before a virus outbreak begins, millions of lives could be saved, lockdowns avoided and the economy preserved."

Professor Marian Knight, Scientific Director for NIHR Infrastructure, described the results as an important advance.

"The remarkable success of this AI-designed 'super-antigen' trial marks a pivotal leap forward in our ability to deliver broad, lasting viral protection."

She added: "This milestone was only made possible through partnerships between the life sciences sector and our world-class NIHR infrastructure in Cambridge and Southampton, whose Clinical Research Facilities provided the vital expertise and environment needed to safely fast-track this innovation, and bring it one big step closer to patients."

Researchers note that SARS-CoV-2 and other Sarbeco coronaviruses remain public health concerns. At the same time, many other viruses continue to circulate in animals and could potentially cross into humans, although it is impossible to predict which virus might emerge next or when.

The project was funded primarily by Innovate UK.

DIOSynVax, short for Digitally Immune Optimised Synthetic Vaccines, was founded in 2017 as a University of Cambridge spinout with support from Cambridge Enterprise, the university's commercialization arm.

The company's vaccine development pipeline also includes candidates targeting seasonal influenza, pandemic influenza threats, hemorrhagic fever viruses, and coronaviruses including SARS-CoV-2.

Jonathan Heeney is Professor of Comparative Pathology at the University of Cambridge and a Fellow of Darwin College.

Journal Reference:

1. Alasdair PS Munro, Matteo Ferrari, Rebecca Kinsley, Daniel Egan, Sneha Vishwanath, Thomas Bower, Andrew Chan, Matthew Davies, Joanne Marie M. Del Rosario, Ron Moss, Yvanne Enever, Benedict Asbach, Ralf Wagner, Rachel Bousfield, Krishna Chatterjee, Victoria Cornelius, Saul N. Faust, Jonathan L. Heeney. A phase I, needle free, dose escalation clinical trial of pEVAC-PS, a candidate pan-Sarbecovirus Vaccine. Journal of Infection, 2026; 92 (6): 106759 DOI: 10.1016/j.jinf.2026.106759

Courtesy:

University of Cambridge. "AI-designed universal coronavirus vaccine passes first human trial." ScienceDaily. ScienceDaily, 5 June 2026. <www.sciencedaily.com/releases/2026/06/260605023357.htm>.