Two studies on respiratory syncytial virus (RSV) protection conclude that vaccine effectiveness against infection and related health care use drops over 18 months in US veterans and that the effectiveness of the long-acting monoclonal antibody preventive nirsevimab is strong in hospitalized European children younger than two years but wanes over seven months.

Older adults and infants are especially vulnerable to severe RSV, with possible complications of bronchiolitis, pneumonia, and sepsis.

Boosters may be needed for older adults

The first study, led by researchers from the Veterans Affairs Portland Health Care System, used a target-trial emulation design to examine the vaccine effectiveness (VE) of one dose of the Abrysvo RSV vaccine in 288,111 US veterans immunized from September 2023 to March 2024, with a median follow-up of 15.8 months. 

The veterans, who were 60 years and older, were matched with as many as four of one million unvaccinated controls in seven monthly, nested sequential trials during two respiratory illness seasons. Men made up 94.5% of participants in both groups, and the median age was 76.1 years.

The findings were published in JAMA Internal Medicine.

Reductions were most notable among immunocompromised persons, suggesting the need to review whether additional vaccine doses may benefit certain risk groups.

VE against RSV infection dropped from 82.5% in the first month to 59.4% over the next 17 months. In the same period, VE fell from 84.9% to 60.5% against emergency department visits, from 88.9% to 57.3% against hospitalization, and from 92.5% to 71.9% against intensive care unit admission. For veterans with weakened immune systems (immunocompromise), VE against RSV infection declined from 75.2% to 39.7% over the same period. 

“The study found that RSV vaccination was effective in preventing RSV illness and associated health care use but that protection decreased over 2 seasons,” the study authors concluded. “Reductions were most notable among immunocompromised persons, suggesting the need to review whether additional vaccine doses may benefit certain risk groups.”

In an editorial in the same journal, Editorial Fellow Anna Hung, PhD, of Duke University, and Associate Editor Lona Mody, MD, of the University of Michigan, noted that, despite the Centers for Disease Control and Prevention’s recommendation for a single dose for anyone aged 75 and older and those aged 60 to 74 years at increased risk for severe disease, less than half of either group receives the vaccine.

“This low uptake can be explained by various reasons including relative recency of development of the vaccine, lack of awareness of the seriousness and frequency of RSV infection, a hazy shared clinical decision-making model, access barriers, a general vaccine fatigue, and lack of clear guidance to clinicians,” they wrote. 

They added that the greater decline in VE among immunocompromised veterans suggests the need for RSV boosters. “Experts will need to evaluate this evidence carefully to update guidance,” they wrote.

85% protection in first month after nirsevimab

For the second study, a pilot published in Eurosurveillance, European researchers analyzed the effectiveness of nirsevimab (Beyfortus) against RSV infection in 2,201 hospitalized children younger than two years in the 2024-25 respiratory virus season.

The study team conducted the test-negative case-control study in Belgium, Portugal, and Spain to compare the status of 791 toddlers hospitalized with confirmed RSV and 1,410 control patients hospitalized for a non-RSV respiratory infection. In total, 35% of infected children and 62% of controls had received nirsevimab.

Real-world studies remain important to address key public health questions, such as whether early-immunised infants remain protected throughout the entire RSV season, the IE by RSV type, and among older high-risk children.

Nirsevimab is recommended for preventing RSV lower respiratory tract infection in infants younger than one year in their first RSV season and in toddlers younger than 24 months at high risk for severe RSV in their second season.

Pooled overall immunization effectiveness (IE) was 79%, declining from 85% in the first month to 78% at 30 to 89 days post-vaccination and 69% at 90 to 215 days. Among infants up to six months old, the overall IE was 80%, falling from 85% in the first month to 78% at 30 to 89 days and from 53% at 90 to 215 days. Overall IE in children aged seven to 23 months was 74%, with wide confidence intervals, indicating considerable uncertainty.

“High long-acting monoclonal antibody IE (79%) was confirmed for the 2024/25 season,” the study authors wrote. “A core European Union 2025–26 protocol has been developed based on lessons learned from this pilot study to improve data collection, increase the sample size at the site level and extend the study to more sites for more precise estimates by time since immunisation.”

“Real-world studies remain important to address key public health questions, such as whether early-immunised infants remain protected throughout the entire RSV season, the IE by RSV type, and among older high-risk children,” they added.