Editorial: Surveillance of Seasonal Respiratory Syncytial Virus (RSV) Infection in Children and Vulnerable Adults Drives Vaccine Development and New Immunization Programs

Respiratory syncytial virus (RSV) infection remains a significant global health problem, particularly affecting infants less than five years of age who are susceptible to severe RSV disease [1,2]. RSV infection in infants results in an estimated 3.6 million hospital admissions and up to 102,000 infant deaths annually [2]. Severe RSV disease affects infants <6 months of age, resulting in 33% of the hospital admissions for RSV infection and 46% of the deaths in children in the under-five age group [3]. Also, RSV is an important cause of lower respiratory tract infection in older adults, particularly frail older adults and those with underlying chronic medical conditions [4]. In 2020, an analysis of published data showed that RSV was the cause of between 1–10% of influenza-like acute respiratory tract illness in adults ≥50 years worldwide [5]. Annually in the US, RSV infection is associated with approximately 60,000–160,000 hospital admissions and 6,000–10,000 deaths in patients ≥65 years of age [6,7]. However, because of challenges associated with conducting RSV reverse-transcription polymerase chain reaction (RT-PCR) testing and inconsistent reporting, the disease burden from RSV infection in adults is likely to be much more significant [8,9].

Recent winter seasons in the northern hemisphere have shown an increased incidence of vaccine-preventable viral infections, including SARS-CoV-2, influenza, measles, and RSV in adults and children [10]. The vulnerability of adults with immune suppression and the elderly to RSV infection is recognized, with vaccination targeted at this adult population [11,12]. In the US, in the winter season, RSV is associated with up to 12% of medically attended acute respiratory tract infections in adults and is the third most commonly diagnosed respiratory virus infection in hospitalized patients [13]. In 2023, in the US, there were an estimated 60,000–160,000 hospitalizations and 6000–10,000 deaths associated with RSV infection in adults aged ≥65 years of age, with the highest rates in those aged ≥75 years [12].

In December 2023, the US Centers for Disease Control and Prevention (CDC) published the 2024 Advisory Committee on Immunization Practices (ACIP) Adult Immunization Schedule with new recommendations and new vaccine schedules [14]. There are currently three available vaccines for the prevention of RSV infection in elderly and vulnerable adults that include an AS01E-adjuvanted RSV prefusion F vaccine (Arexvy), a non-adjuvanted bivalent RSV prefusion F vaccine (Abrysvo), and an mRNA vaccine (MResvia) [14]. Arexvy is an adjuvanted vaccine with recombinant RSV glycoprotein F stabilized in the prefusion conformation [15]. The adjuvanted RSV vaccine, Arexvy, is the first approved vaccine to prevent lower respiratory tract infection caused by RSV in adults ≥60 years [15]. Arexvy offers approximately 83% protection in adults and appears to maintain effectiveness for up to two RSV seasons [15]. The vaccine was generally well tolerated in clinical trials, with the most frequently reported adverse events including mild to moderate injection site pain, myalgia, fatigue, arthralgia, and headache [15]. Until the development and approval of vaccines to prevent RSV infection, which have been available only relatively recently, there was one licensed preventive agent, the monoclonal antibody palivizumab (Synagis) [16,17]. However, palivizumab (Synagis) requires monthly intramuscular injections and is costly, which means that it is only offered to infants at high risk and leaves other children vulnerable to infection [3].

Recent approaches to preventing RSV infection in infants include maternal vaccination as part of antenatal care. Currently, two vaccines are available to prevent severe RSV disease in infants: a maternal vaccine, the non-adjuvanted vaccine, Abrysvo, and a long-acting monoclonal antibody, nirsevimab (Beyfortus), either of which can protect the infant [18,19]. Seasonal use of Abrysvo is recommended for women between 32–36 weeks of pregnancy, which also protects the infant [20,21]. The maternal vaccine, Abrysvo, effectively protects against RSV infection during the infant’s first six months [22]. The long-acting anti-RSV monoclonal antibody, nirsevimab (Beyfortus), has an extended half-life, targets the surface F protein of RSV, and is 74.5% effective at reducing RSV disease in late-preterm and term infants [19,23]. Nirsevimab (Beyfortus) was approved by the US Food and Drug Administration (FDA) in 2023 [19,23]. Nirsevimab (Beyfortus) is recommended for infants <8 months of age, infants born to mothers vaccinated >14 days before birth, or infants born to mothers with an inadequate vaccine immune response or have immune suppression, and is also recommended for unvaccinated mothers [20,21]. The monoclonal antibody, palivizumab, is given to children <24 months of age with high-risk medical conditions [20,21,24,25]. Recent modeling and clinical studies have evaluated the benefits of these RSV vaccines and have begun to address some of the concerns regarding their safety and efficacy in children, pregnant women, and the elderly.

In 2024, Hodgson and colleagues published the findings from a modeling study to compare the single-dose long-acting monoclonal antibody and the maternal vaccine to prevent RSV infection [26]. The study aimed to select new RSV intervention programs for England and Wales for large-scale vaccine implementation and to compare the costs and health benefits [26]. For infants <6 months old in England and Wales, they predicted 60% coverage with a year-round maternal vaccination program to prevent 32% of hospital admissions [26]. They found that a year-round long-acting monoclonal antibody program with 90% coverage would prevent 57% of hospital admissions due to RSV [26]. Modeling also showed that the maternal vaccination program resulted in additional health benefits for pregnant women and that programs for both vaccines were cost-effective by reducing the disease burden in the infant population [26]. This modeling and cost-effectiveness analysis was used to inform the UK Health Security Agency (HSA) and Joint Committee for Vaccination and Immunisation (JCVI) in the preparation of current recommendations for an RSV immunization program to protect newborns and infants [26,27]. This new RSV vaccination program in the UK was predicted to prevent 5,000 hospitalizations and 15,000 emergency department attendances for infants during the winter of 2024/2025 [26]. The same modeling methods have shown that implementing the first season of a catch-up vaccination program for older adults could prevent up to 60,000 cases of symptomatic RSV infections, 15,000 primary care visits, and 2,500 hospital admissions in England and Wales [26]. In September 2024, the UK National Health Service (NHS) began vaccinating pregnant women and older adults ≥75 years [28].

Vaccination to prevent RSV infection has been recommended for immunocompromised ≥60 years, but until recently, efficacy data for RSV vaccination in this population has been limited [29]. In October 2024, Payne and colleagues published the findings from an observational study based on electronic health records that included >10,000 mild and moderately immunocompromised individuals ≥60 years old, which included 46% of cases associated with malignancy [30]. The adjusted effectiveness of vaccination against RSV-associated hospitalizations in the first year of patient follow-up was 73% [30]. Therefore, evidence supports RSV vaccination’s efficacy in immunocompromised individuals ≥60 years old [30].

Maternal vaccination with the non-adjuvanted vaccine, Abrysvo, can reduce the risk of infant morbidity and mortality [31]. Although randomized trials have supported the safety and efficacy of the Abrysvo vaccine, there were some initial reports of a small but increased risk of preterm birth following maternal vaccination [31]. In January 2025, Madhi and colleagues published their final analysis of a global, randomized trial that included more than 7,000 pregnant women who were given Abrysvo or placebo (NCT04424316) [31]. The findings showed that preterm birth rates were similar for women vaccinated with Abrysvo when compared with women given a placebo (5.7% versus 4.7%) and with most of the preterm births occurring at ≥34 weeks of gestation [31]. These findings support current recommendations for maternal vaccination of eligible pregnant women.

In January 2025, the FDA issued a warning about Guillain-Barré syndrome in adults receiving either of the two glycoprotein subunit RSV vaccines, the adjuvanted RSV vaccine, Arexvy, or the non-adjuvanted vaccine, Abrysvo, [32]. Observational data analysis from people aged ≥65 years showed an estimated 7 excess cases of Guillain-Barré syndrome per million doses of Arexvy and 9 excess cases of Guillain-Barré syndrome per million doses of Abrysvo [32]. However, to put these complications into perspective, morbidity and mortality from RSV infection in adults ≥65 years in the US result in between 60,000–160,000 hospitalizations and 6,000–10,000 deaths each year with an annual hospitalization cost burden of more than $1 billion [6,33].

Conclusions

Global surveillance of seasonal respiratory tract infections has identified a significantly increasing trend in RSV infection in infants and vulnerable and elderly adults. The development of new vaccines has been rapid. Safe and effective approaches to immunization have resulted in new immunization schedules and recommendations for infants, children, pregnant women, and vulnerable adults, including the elderly.