Future therapies for respiratory syncytial virus (RSV) must target both the virus and its immune response to ensure babies get the best possible outcomes, finds a new study by researchers at UCL and Great Ormond Street Hospital for Children (GOSH).
RSV is the biggest cause of serious illness in babies, with over three million hospital admissions worldwide because of the virus every year.
It causes wheezing and breathing difficulties, and in the worst cases babies end up in intensive care. Despite this, treatment options for infants who develop severe disease remain extremely limited.
As part of the new study, published in Nature Communications and funded by Animal Free Research UK and UK Research and Innovation (UKRI), researchers built a new lab model of baby lungs to show why RSV makes infants so much sicker than adults and allow them to test new treatments before they reach patients.
The miniature model of a baby's airways was created using real infant airway cells, blood vessel cells and neutrophils (a type of white blood cell that acts as the immune system's primary response to infection).
To compare with an adult response to RSV, the research team also made a model of an adult's airways.
Dr Claire Smith (UCL Great Ormond Street Institute of Child Health), who led the study, said: "This model allows us to watch early immune responses unfold and study them in a human setting that reflects the infant airway. That's something animal models often struggle to capture, especially when it comes to age-specific effects."
When the models were infected with RSV, the team found that baby airway cells attracted far more white blood cells than adult airway cells did. This influx can block babies' small airways and make it harder for them to breathe.
Neutrophils normally circulate in the blood but enter lung tissue in response to infection. In the baby airway model, researchers found that the neutrophils that entered the lung tissue were more activated and triggered a stronger inflammatory reaction than in the adult model.
This effect depended on the immune cells physically moving through the infected tissue, not just responding to chemical signals released by it, making this type of model essential for studying it.
This suggests it's the infant airway itself, not just the virus, that ramps up the immune response and causes damage to the lungs.
First author, Dr Machaela Palor (UCL Great Ormond Street Institute of Child Health), said: "These findings help explain why RSV is often much more severe in infants than in adults. The paediatric airway actively shapes how immune cells behave during the infection."
The researchers then tested two antiviral drugs (remdesivir and RSV604). Both stopped the virus from multiplying, but only RSV604 also calmed the overactive immune response, reducing levels of a key inflammatory protein released by white blood cells - high levels of which are linked to more severe RSV disease in babies.
Remdesivir had no effect on this, suggesting that not all antivirals are equal when it comes to protecting the infant airway from immune-driven damage.
This suggests that treating severe RSV in babies may require more than just stopping the virus – it may also be important to calm an overactive immune response.
The researchers hope their findings and the new approach to research on RSV will accelerate the development of treatments better tailored to infants.
Dr Smith said: "Our model gives us a way to assess both sides of the problem at once. We can not only ask whether the drug stops the virus but also whether it helps control immune response in the infant airway.
"This work reinforces the idea that age matters in respiratory infection. Understanding how infant airways shape immune responses will be key to designing safer and more effective RSV treatments."
Carla Owen, CEO, Animal Free Research UK, said: "Dr Smith and Dr Palor's groundbreaking study shows the power of human-specific research to make breakthroughs for patients. Their sophisticated human model brings hope to families without using animals. This is science at is best. We are proud to have funded this innovative work, and we look forward to seeing the impact this will have on improving treatment for babies affected by RSV."
