Credit: UM School of Medicine
Acute respiratory infections remain one of the leading causes of hospitalization in children worldwide. Last year, at least 1 million people in the U.S. were hospitalized for respiratory virus illnesses like the flu or COVID-19, according to the CDC. Many of these individuals were at higher risk of getting infections due to living or working around young children who contract more respiratory infections.
While vaccines are effective—and significantly reduce the risk of death—the immune system can still falter in instances of repeated exposure to viruses.
That’s why a new clinical trial is testing a virus-agnostic intranasal spray designed to boost immune defenses.
Led by researchers at the University of Maryland in collaboration with manufacturer ENA Respiratory, this ENA Respiratory this randomized double-blind Phase 2 trial aims to enroll 1,100 healthy adults ages 18 to 45 years who are at increased risk of upper respiratory virus infections due to exposure to young children or frequent close contact with others. Participants will be randomly assigned to receive the intranasal spray, called INNA-051, or a placebo spray to determine if INNA-051 is safe and works better than the placebo at boosting the immune response and preventing illness.
“Instead of targeting a single virus, INNA-051 strengthens the body’s early immune defenses, which may help mitigate disease caused by multiple respiratory pathogens,” said Justin Ortiz, MD, professor of medicine and a respiratory illness specialist who is the principal investigator for the trial.
A non-vaccine, intranasal spray, INNA-051 works as a prophylactic drug designed to be taken weekly during cold and flu season. It is a TLR2/6 agonist, which works by priming the immune system’s first line of defense in an effort to accelerate the clearance of harmful germs from nasal passages before viruses can get a foothold in the body and cause an infection.
INNA-051 is virus-agnostic, meaning that it can potentially help protect against a wide array of viruses, and acts in the nasal passages—the site of initial replication of common respiratory viruses such as the flu, colds and COVID-19. The study will investigate whether INNA-051 can reduce the severity or likelihood of illness during respiratory virus season.
Respiratory infection trends in children
Targeting the immune system rather than a specific virus is an interesting approach as it offers a solution for emerging viruses for which vaccines or direct-acting antivirals have limitations or do not yet exist. This approach also caters to the shifts pediatric medicine has seen in regard to respiratory infection trends post-COVID.
In a new study published in Pediatric Investigation, researchers in China explored how the pandemic changed respiratory infection trends in children in Wenzhou and Ningbo, two coastal cities in eastern China with similar climates.
The team retrospectively analyzed respiratory samples collected between March 2021 and February 2024 from 73,096 pediatric patients hospitalized with acute respiratory tract infections in the two cities. The researchers screened each sample for 13 non-bacterial respiratory pathogens, including influenza viruses, respiratory syncytial virus (RSV), rhinovirus, human coronaviruses and Mycoplasma pneumoniae. Advanced statistical and time-series models were then used to examine co-infections and pathogen interactions over time.
During periods of non-pharmaceutical interventions, the overall detection of respiratory pathogens dropped by more than 56%, underscoring how effective masking, social distancing and reduced mobility were at suppressing transmission. After restrictions were revoked, however, detection rates rebounded by over 75%, with some pathogens returning at levels higher than before the pandemic.
The most striking increase involved Mycoplasma pneumoniae, an atypical bacterium that commonly causes pneumonia in children. Its detection rate surged from 5% during the pandemic to 35% afterward, making it the most frequently detected pathogen in the post-pandemic period.
Additionally, the study revealed a major shift in how respiratory pathogens interacted. After the pandemic, negative correlations between pathogens were reported to have grown stronger, where the presence of one pathogen was associated with reduced detection rates of another.
One consistent finding was a persistent negative relationship between the Influenza B virus and Mycoplasma pneumoniae. When Influenza B activity peaked, Mycoplasma pneumoniae detections temporarily declined, suggesting a phenomenon known as pathogen interference.
“This pattern hints that infection with one pathogen may briefly suppress another, possibly through immune responses like interferon release,” said study co-author Shunhang Wen of Yuying Children’s Hospital of Wenzhou Medical University. “Understanding these dynamics could help clinicians anticipate shifts during outbreaks.”
The researchers say the findings highlight the importance of ongoing virus surveillance.
“The post-pandemic era is not a return to the old normal. Respiratory pathogens are interacting in new ways, and public health systems need to be prepared for unexpected patterns of childhood infections,” said study co-author Hailin Zhang of Yuying Children’s Hospital of Wenzhou Medical University.