Bacterial meningitis can cause severe brain damage even when patients receive antibiotic treatment promptly. Researchers at Karolinska Institutet have now developed tiny biological vesicles that, in animal studies, were able to capture bacterial toxins, protect neurons, reduce inflammation and delay the progression of the disease. The findings are published in the scientific journal Journal of Extracellular Vesicles.
Pneumococcal meningitis is a life-threatening infectious disease of the central nervous system caused by the bacterium Streptococcus pneumoniae. Despite treatment with antibiotics and anti-inflammatory drugs, around one in three patients are left with long-term neurological complications. According to the researchers, one reason is that antibiotics may take time to reach the brain and do not neutralize pneumolysin, a toxin released by the bacteria that contributes to neuronal damage and inflammation.
In the new study, researchers investigated whether extracellular vesicles, small membrane-bound particles naturally produced by cells, could be used to protect the brain during infection. The vesicles were engineered in different ways, including a version designed to target neurons more efficiently and suppress severe neuroinflammation. They were then tested in laboratory-grown neuronal and brain immune cells, as well in a preclinical meningitis mouse model.
Extracellular vesicles acting as decoys
The experiments showed that all types of vesicles could bind to and sequester pneumolysin before it damaged neurons. They also reduced the ability of the bacteria to attach to neurons and lowered harmful inflammatory signals in both cell-based experiments and in vivo.
When given through the bloodstream, the vesicles were able to reach the brain in infected mice. Treatment delayed the onset of severe disease and increased survival compared with untreated animals.
The vesicle variant engineered with RVG peptides, which help target neurons in the nervous system, and IL6-decoy to selectively inhibit IL-6 trans-signalling had the strongest neuroprotective and anti-inflammatory effects in both the brain and the rest of the body.
"Our results suggest that the extracellular vesicles act as decoys, capturing pneumolysin before the toxin can reach and damage neurons. IImportantly, the same biomaterial also act as suppressor of severe and harmful inflammation," says Associate Professor Federico Iovino , group leader at the Department of Neuroscience at Karolinska Institutet and last author of the study.
Further studies required
The treatment has not yet been tested together with antibiotics, which are the standard treatment for patients. The researchers therefore stress that further studies are needed before the method can be evaluated in humans.
"We hope that extracellular vesicles could eventually become a complement to current treatments for pneumococcal meningitis, but more research is required before any clinical application can be considered, and this is what my lab is currently working on" says Federico Iovino.
"These great results were possible thanks to the great collaboration that my lab established with the research groups of Assistant Professor Oscar Wiklander and Professor Samir EL Andaloussi at the Department of Laboratory Medicine , Karolinska Institutet," he continues
The study was funded by the Swedish Research Council, StratNeuro, Karolinska Institutet, the Bjarne Ahlström Memorial Fund, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the Clas Groschinsky Foundation, HRH Crown Princess Lovisa's Association for Children's Health, Karolinska Institutet, the Magnus Bergvall Foundation, the Åhlén Foundation, the Wera Ekström Fund for Paediatric Research, the Jane and Dan Olsson Foundation, and the Tysta Skolan Foundation.
Publication
Kristine Farmen, Doste R. Mamand, Miguel Tofiño-Vian, Georgia Yfanti, Xiuming Liang, Houze Zhou, Vicky W. Q. Hou, Samir El Andaloussi, Oscar P. B. Wiklander, Federico Iovino
Journal of Extracellular Vesicles, 11 September 2026, doi.org/10.1002/jev2.70369
