Durability of Respiratory Syncytial Virus Vaccine Effectiveness Among US Veterans
What is the long-term effectiveness of a single respiratory syncytial virus (RSV) vaccine dose against RSV illness and associated health care use?
College of Health researcher(s)
Abstract
Importance
A single respiratory syncytial virus (RSV) vaccine dose is recommended for older adults and persons at increased risk for severe RSV. Clinical information on the long-term effectiveness of RSV vaccines is needed.
Objective
To determine the effectiveness of RSV vaccination over 2 respiratory illness seasons.
Design, Setting, and Participants
This target trial emulation used data from the Veterans Health Administration and included veterans 60 years and older who were eligible for RSV vaccination from September 2023 to March 2024.
Exposure
A single dose of a recombinant stabilized prefusion F protein RSV vaccine vs no RSV vaccination.
Main Outcomes and Measures
Eligible vaccine recipients were matched with up to 4 unvaccinated individuals in 7 monthly, nested sequential trials from September 1, 2023, to March 31, 2024. Outcomes were ascertained through March 31, 2025. The primary outcome was any positive RSV test result from day 14 following the matched index date. Secondary outcomes included RSV-associated emergency department or urgent care visits, hospitalizations, or intensive care unit admissions. Vaccine effectiveness was estimated as 100 × (1 – risk ratio).
Results
A total of 288 111 vaccinated individuals were matched to 1 075 893 unique control individuals, weighted equally to represent 576 222 individuals, and followed up for a median of 15.8 months (IQR, 14.5-17.0). Across both groups, 544 364 of 576 222 veterans (94.5%) were male, and the median age was 76.1 years (IQR, 71.6-80.0). Vaccine effectiveness against documented RSV infections decreased from 82.5% (95% CI, 77.5%-86.9%) over 0 to 1 month to 59.4% (95% CI, 55.6%-63.5%) over 0 to 18 months of follow-up. During the same period, effectiveness decreased from 84.9% (95% CI, 78.4%-90.2%) to 60.5% (95% CI, 56.4%-65.7%) for emergency visits and 88.9% (95% CI, 77.9%-95.7%) to 57.3% (95% CI, 47.3%-66.4%) for hospitalizations and was 92.5% (95% CI, 61.1%-100.0%) and 71.9% (95% CI, 42.8%-90.0%) for intensive care unit admissions. Among immunocompromised individuals, protection against documented infections decreased from 75.2% (95% CI, 52.5%-89.3%) to 39.7% (95% CI, 23.9%-52.7%).
Conclusions and Relevance
The study found that RSV vaccination was effective in preventing RSV illness and associated health care use but that protection decreased over 2 seasons. Reductions were most notable among immunocompromised persons, suggesting the need to review whether additional vaccine doses may benefit certain risk groups.
Understanding the Long-Term Effectiveness of the RSV Vaccine: A 5-Point FAQ
Respiratory Syncytial Virus (RSV) poses a significant health risk to older adults, often leading to serious respiratory illness. The introduction of RSV vaccines marked a major public health achievement, but crucial questions remain about how long their protection lasts in a real-world setting. A major new study published in JAMA Internal Medicine provides critical insights into the durability of a single vaccine dose. This FAQ distills the key findings from this research, making its important conclusions on vaccine effectiveness accessible to a general science reader.
What was this study investigating?
Initial clinical trials are essential for establishing a vaccine's safety and efficacy, but the true test of its public health value comes from long-term, real-world evidence. Understanding how a vaccine performs over multiple seasons in a large and diverse population is a critical factor for shaping official health recommendations. This study aimed to determine how effective a single dose of the RSV vaccine is over a period covering two full respiratory illness seasons. To accomplish this, researchers used a "target trial emulation," a powerful method that uses comprehensive electronic health records to mimic a large-scale clinical trial. The study drew data from the Veterans Health Administration (VHA), whose large and comprehensive EHR infrastructure is uniquely suited for this type of robust, real-world analysis. Researchers analyzed a cohort of nearly 290,000 vaccinated veterans aged 60 and older, comparing their health outcomes to a carefully matched group of unvaccinated veterans to measure the vaccine's protective benefit. This large-scale setup allowed researchers to generate robust evidence on the vaccine's ability to prevent illness over an extended period.
What did the study find about the vaccine's overall effectiveness?
The ultimate goal of a vaccine is not just to prevent infection but, more importantly, to prevent severe outcomes that require medical attention and hospitalization. Vaccine effectiveness is therefore measured by its ability to reduce the burden of disease, from documented positive tests to emergency room visits and inpatient care. The study confirmed that a single dose of the RSV vaccine is highly effective at preventing documented RSV illness and the associated need for healthcare, providing strong defense at the start of the respiratory virus season. The data revealed impressive levels of initial protection against a range of outcomes:
- Vaccine effectiveness against any documented RSV infection was 82.5% in the first month.
- Effectiveness against RSV-associated hospitalizations was 88.9% in the first month.
- Effectiveness against RSV-associated ICU admissions was even higher at 92.5% in the first month.
While this initial performance is impressive, a key question for public health is how this high level of protection holds up over time, a concept central to the study's investigation.
How long does the vaccine's protection last?
Waning immunity is a common and expected phenomenon for many vaccines, where the level of protection gradually decreases over time after vaccination. This does not mean the vaccine stops working, but that its effectiveness is reduced. Quantifying the rate of this decline is essential for public health experts to determine future vaccination strategies, such as whether periodic booster shots might be necessary. The study found that while the RSV vaccine is highly effective at first, this protection wanes over an extended follow-up period of about 18 months, covering two respiratory seasons. The effectiveness against both infection and hospitalization decreased from its initial peak, though it still offered significant protection compared to being unvaccinated.
The study quantified this decline with the following data:
- Against documented infection: Effectiveness decreased from an initial high of 82.5% (at 0-1 month) to a cumulative effectiveness of 59.4% over the entire 0-to-18-month follow-up.
- Against hospitalization: Effectiveness similarly decreased from 88.9% (at 0-1 month) to a cumulative effectiveness of 57.3% over the entire 0-to-18-month follow-up.
This finding is crucial, as it indicates that while protection persists into a second season, it is not as robust as it was initially, and this decline was not uniform across all patient groups.
Does the vaccine protect everyone equally over time?
Evaluating vaccine performance in specific high-risk subgroups is a critical component of public health research. Individuals with weakened immune systems or other underlying health conditions are often the most susceptible to severe disease, yet they are frequently excluded from the initial clinical trials used for vaccine approval. This study found that the durability of vaccine protection was not the same across all groups, with the most significant reduction in effectiveness over time observed among key high-risk populations.
For immunocompromised individuals, protection declined more steeply compared to those who were not immunocompromised. The data shows a stark contrast:
- Protection against documented RSV infection for this group dropped from 75.2% in the first month to a cumulative effectiveness of just 39.7% over the full 18-month study period.
- For comparison, nonimmunocompromised individuals maintained a higher cumulative effectiveness of 60.7% against infection over the same timeframe.
The study noted a similar pattern in the very elderly, identifying adults 80 years and older as another group with lower long-term protection, with an estimated cumulative effectiveness of around 50% over 18 months. This demonstrates that while the vaccine provides an initial benefit to all, the most vulnerable may lose a substantial degree of protection as they enter a second respiratory season.
What is the main takeaway from this research?
As public health officials work to refine vaccination guidelines, they rely on robust, real-world evidence to make the best possible recommendations. This study provides a vital piece of that puzzle, offering clear data on how the RSV vaccine performs in older adults beyond the first season. The core conclusion is that a single dose of the current RSV vaccine provides significant protection against RSV illness and hospitalization, but this protection clearly declines over the course of two respiratory seasons.
The most critical implication is that this reduction in effectiveness is most pronounced in high-risk groups, particularly among immunocompromised persons and the very elderly. By providing clear evidence of this waning immunity, these findings establish the need to formally evaluate the potential benefits and risks of a second vaccine dose for certain at-risk groups to ensure they remain protected season after season.