RSV vaccination uptake by the end of the 2024-25 respiratory virus season among adults aged 60-74years at increased risk of severe RSV and adults aged ≥75years.

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4+ Tcells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-γ (IFN-γ) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.

IntroductionThe burden of respiratory syncytial virus (RSV) disease is substantial among adults aged ≥ 60 years and adults with risk factors for severe RSV. This study assessed the knowledge, attitudes, and practices of healthcare professionals (HCPs) related to RSV disease and vaccination, with a focus on adults aged ≥ 60 years.MethodsDuring November 14–30, 2023, a cross-sectional, web-based survey was administered to HCPs, targeting a total of 600 primary care physicians (PCPs), specialist physicians, nurse practitioners (NPs)/physician assistants (PAs), and pharmacists. Survey questions evaluated knowledge about RSV disease, vaccines, and vaccination recommendations; RSV-related attitudes and perceptions; and RSV vaccination practices. Responses were analyzed descriptively, overall and by HCP subgroup. Multivariable logistic regression models were used to explore HCP characteristics associated with RSV vaccination knowledge and practices.ResultsOf the 603 respondents (148 PCPs, 151 specialist physicians, 150 NPs/PAs, and 154 pharmacists), 63.0% were very familiar with RSV disease in patients aged ≥ 60 years. Although most HCPs recognized the benefits of RSV vaccination within this patient population, many HCPs were not fully knowledgeable about RSV vaccine recommendations, and 33.5% had not recommended, prescribed, or administered any RSV vaccine to patients aged ≥ 60 years in the previous 3 months. In multivariable regression analyses, HCP familiarity with RSV disease (among other factors) was consistently associated with RSV vaccination knowledge and practices.ConclusionsThis study characterized RSV disease- and vaccine-related knowledge, attitudes, and practices among HCPs in the United States during the first season of RSV vaccine availability for adults aged ≥ 60 years. These findings can help to inform HCP and patient education efforts to address potential RSV vaccination knowledge gaps and ensure equitable access to RSV vaccines among older adults.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-025-01119-0.

BackgroundIn 2023, respiratory syncytial virus (RSV) vaccines were approved by the United States (US) Food and Drug Administration (FDA) for adults aged ≥60 years and recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) using shared clinical decision-making (SCDM). This study evaluated healthcare professional (HCP) characteristics associated with RSV vaccination knowledge and practices.MethodsA cross-sectional online survey targeting approximately 600 HCPs was conducted in November 2023 to assess HCP knowledge, attitudes, and practices related to older adult RSV vaccination. Three logistic regression models used these survey data to explore HCP characteristics associated with RSV vaccination knowledge and practices (e.g., likelihood of knowing FDA indication and ACIP recommendation). The models included HCP type as a covariate a priori, with other covariates determined using backwards selection with a prespecified stay criterion (P < 0.1).ResultsThe survey was completed by 603 HCPs (Table 1). HCPs had higher odds of being knowledgeable about the FDA indication and ACIP recommendation for older adult RSV vaccination if their workplace stocked RSV vaccine(s); odds were lower if HCPs were least familiar with RSV disease or had a higher percentage of non-White adult patients (Table 2). Odds of initiating RSV vaccination conversations with ≤5% of older adult patients were higher among HCPs who were less familiar with RSV disease, felt less confident in SCDM conversations, and perceived RSV protection to be less important than other respiratory infections (Table 3). Being less familiar with RSV disease was also associated with higher odds of not recommending/administering RSV vaccines to any older adults in the past 3 months (Table 4).ConclusionHCP familiarity with older adult RSV disease was associated with RSV vaccination knowledge and practices, highlighting the importance of continued RSV disease awareness efforts. Results can be used to tailor these efforts towards HCPs with potential vaccination knowledge and practice gaps to help ensure equitable RSV vaccination access across older adults.FUNDING: GSK (study identifier: VEO-000726)DisclosuresElizabeth M. La, PhD, GSK: employee|GSK: Stocks/Bonds (Private Company) David Singer, PharmD, MS, GSK: employee|GSK: Stocks/Bonds (Public Company) Eric Davenport, MStat, MEcon, GSK: study funding Andrea Harmelink, PhD, FNP, GSK: Stocks/Bonds (Public Company)

Respiratory syncytial virus (RSV) remains one of the most important infectious causes of hospitalization in infants and children. This enveloped, RNA virus produces predictable yearly outbreaks of disease that typically peak between January and February in countries in the northern hemisphere.1 The outcome of RSV infection varies from mild upper respiratory tract infection in approximately 75% of infected infants and young children to severe life-threatening disease in a small percent of infected patients.2 In the United States, RSV lower respiratory tract infection accounts for nearly 50% of hospitalizations due to bronchiolitis and 25% of hospitalizations due to pneumonia.1 Serologic surveys suggest that by 2 years of age, more than 90% of all children have been infected by RSV.3 Whether RSV infection early in life predisposes to subsequent reactive airway disease remains an unanswered question. Reinfection is common, indicating that immunity to RSV following natural infection is less than complete.4-6RSV lower respiratory tract disease occurs primarily in infants under 2 years of age; most infants who require hospitalization are previously healthy infants less than 6 months of age. Premature infants, infants born with congenital heart disease, and those with chronic lung disease (such as bronchopulmonary dysplasia [BPD]) constitute additional high-risk groups with high rates of hospitalization due to RSV infection.7-13 A recent report describes RSV mortality rates among such hospitalized infants of 4% to 5%.14Pre-engraftment bone marrow transplant recipients, solid organ transplant recipients, and lymphopenic children receiving chemotherapy appear to suffer even higher mortality rates, although prospective data are not available.15 Morbidity in these groups is also great; the average hospital stay and intensity of care for such children may be several times that of previously healthy infants.Despite the importance of RSV as a pathogen in the pediatric age group, options for treatment and prevention of RSV disease are limited. Aerosolized ribavirin was licensed in 1986 for treatment of children hospitalized with severe RSV lower respiratory tract infection. The efficacy of ribavirin therapy remains controversial despite the growing number of carefully conducted trials.16 Factors that complicate evaluation of antiviral therapy include the self-limited nature of most viral respiratory tract illness, and variation in the natural history of RSV disease from patient to patient. These variables make it difficult to select and define distinct endpoints that can be used to evaluate differences between treatment and control groups.Active immunization to prevent severe RSV disease has not yet been successful. Persistent concern regarding vaccine safety in the young infant is the result of an unanticipated reaction to a formalin inactivated RSV vaccine used in trials conducted in the early 1960s.17-19 Recipients (less than 12 months of age) of the inactivated RSV vaccine experienced higher mortality and morbidity rates upon subsequent RSV infection than did infants who received the control vaccine. The immunologic mechanism for this reaction remains unclear although there appears to have been an aberration in both the cellular and humoral response to the vaccine. Vaccine development is also complicated by the limited ability of infants to mount an immune response to RSV glycoprotein antigens. Furthermore, the presence of maternal neutralizing antibodies may attenuate an active immune response in a vaccinated infant. Despite current efforts to develop subunit vaccines, peptide vaccines, or live attenuated RSV vaccines, it is unlikely that active immunization for infants will be available in the near future.20As an alternative to active immunization against RSV, several approaches to passive immunization in high-risk infants have been evaluated. Clinical trials were first conducted using standard intravenous immune globulin (IGIV). Two randomized controlled trials involving monthly infusions of standard IGIV to high-risk infants failed to demonstrate a reduction in hospitalization rates due to RSV.2122 This lack of efficacy was most likely due to a failure to attain adequate peak and trough RSV neutralizing antibody titers. With the development of an RSV-enriched immune globulin in the late 1980s (RSV-IGIV), it became possible to achieve sufficiently high neutralizing antibody levels in the outpatient setting with infusion of a reasonable fluid volume (15 mL/kg). The first RSV-IGIV prophylaxis trial (National Institute of Allergy and Infectious Disease [NIAID] trial) published in 1993 was conducted over three respiratory virus seasons and included 249 children with prematurity, chronic lung disease or congenital heart disease.23 Children who received 750 mg/kg/dose of RSV-IGIV had a 63% reduction in RSV hospitalizations and a 63% reduction in RSV hospital days relative to control patients receiving no RSV-IGIV. A second prophylaxis trial using RSV-IGIV (PREVENT trial), was conducted over one respiratory virus season and included 510 premature infants with and without BPD.24 This trial demonstrated a 41% reduction in RSV hospitalizations and a 53% reduction in RSV hospital days. A third multicenter RSV-IGIV prophylaxis trial involving 416 infants and children (Cardiac trial) failed to show an overall reduction in RSV disease severity in children with congenital heart disease (unpublished data). A meta-analysis of children less than 6 months of age from all three prophylaxis trials demonstrated a 47% reduction in RSV-induced hospitalization (95% confidence interval of .28–.82) (P = .006) (Table). However, caution must be observed in interpreting these data. Although there is considerable interest in the evaluation of hospitalization rates in subgroups of infants, none of the three trials were prospectively designed for subgroup analysis.Two additional clinical benefits of polyclonal immune globulin administration were observed in recipients of RSV-IGIV prophylaxis. The PREVENT trial demonstrated a 38% reduction in hospitalization due to respiratory tract infection by any respiratory virus and a 46% reduction in total hospital days due to all respiratory illnesses.24 Further, both the NIAID trial and the PREVENT trial demonstrated a reduction in the incidence of acute otitis media in high-dose RSV-IGIV recipients (750 mg/kg/dose) relative to low-dose or control patients.2425RSV-IGIV use in patients with congenital heart disease has been evaluated in two trials (the NIAID trial and the Cardiac trial) and has involved a total of 516 children. The safety of RSV-IGIV, particularly in children with cyanotic heart disease, is uncertain. There appeared to be an increased incidence in both morbidity and mortality, particularly in association with cardiac surgery in RSV-IGIV recipients with cyanotic heart disease as compared with placebo recipients. The deaths occurred at variable times, up to 3 months following an RSV-IGIV infusion. No explanation has yet been found. At the present time, use of RSV-IGIV should be avoided in children with cyanotic heart disease. Among children with left to right shunts who received RSV-IGIV there was not a statistically significant reduction in the overall incidence of RSV hospitalization relative to the control group. Therefore, based on the currently available data, RSV-IGIV does not appear to be indicated for most children with noncyanotic congenital heart disease. It may be that immunoprophylaxis will be beneficial in those infants with noncyanotic heart disease who also satisfy immunoprophylaxis criteria based on prematurity or the presence of BPD. The role of RSV-IGIV in infants with large left to right shunts with pulmonary hypertension remains uncertain.RSV-neutralizing antibodies are directed mainly against two surface glycoproteins. The G glycoprotein mediates RSV attachment to a cell that will support RSV replication by binding with cellular receptors containing sialic acid. The F glycoprotein mediates fusion of the viral lipid envelope with the plasma membrane of the cell. Although there may be considerable sequence divergence in the G glycoprotein between RSV subgroups, the important neutralizing epitopes of the F glycoprotein appear to be faithfully conserved between RSV strains and over time. There has been interest in the use of monoclonal antibodies for prophylaxis against RSV disease because of the possibility of intramuscular (rather than intravenous) administration. One immunoprophylaxis trial using a humanized immunoglobulin G (IgG) monoclonal antibody was conducted during the 1995–1996 respiratory season. In this large, multicenter, double-blind, randomized, placebo-controlled trial, monoclonal antibody or placebo was administered intramuscularly once a month to preterm infants during the respiratory virus season. The results proved disappointing (unpublished data). Although safe, this monoclonal antibody preparation did not reduce RSV hospitalization rates at the dose administered. A second multicenter prophylaxis trial using a higher dose of a somewhat different humanized murine IgG monoclonal antibody and involving over 1500 patients is currently underway.RSV transmission occurs primarily by direct introduction of virus contaminated secretions onto mucous membranes of the upper airway. Bronchiolitis and pneumonia develop when RSV from the upper airway is aspirated into the lungs. The presence of RSV immunoglobulin A (IgA) nasal antibody may protect infants against the low titer of RSV that initiates infection. Studies in experimental animals demonstrate that intranasal administration of a murine monoclonal IgA directed against the RSV F glycoprotein significantly reduced viral replication in the nasal turbinates and the lungs.2627 Phase III prophylaxis trials to evaluate topical daily instillation of IgA antibody as nose drops are currently in progress in high-risk infants.The severity of RSV infection appears to be a function of both a direct viral cytopathic effect and the immune response of the host. Evidence supporting the concept that antiviral activity alone may not be sufficient to attenuate RSV disease expression comes from the unpublished trial demonstrating little if any benefit from prophylaxis with monoclonal IgG antibody, and from the clinical trials that show little beneficial effect from RSV-IGIV in the treatment of established RSV disease in infants.28 The beneficial effect on RSV disease severity that is derived from immunoprophylaxis with a hyperimmune polyclonal product may not be due to RSV neutralizing antibody alone.29 What other critical functions might be present in RSV-IGIV that are not present in a preparation of monoclonal antibodies? Recognized immunomodulatory functions of standard IGIV include: alteration of cytokine production,30 inhibition of T-cell proliferation in vitro,31 increase in natural killer cell activity,32 increase in antibody dependent cell cytotoxicity,32 and neutralization of superantigen activity.33 How important these or other as yet unrecognized immunomodulatory functions are in the attenuation of RSV disease expression remains to be determined.The cost of immunoprophylaxis with RSV-IGIV (licensed in 1996 by the Food and Drug Administration and sold under the trade name RespiGam) over one respiratory season is approximately $5000.34Therefore, it is important that prophylaxis be reserved for carefully selected infants. A recently published consensus statement reviewed the existing literature on RSV disease in various high-risk groups and offered the following guidelines for selection of RSV-IGIV eligible patients15:It must be remembered that the majority of children hospitalized due to RSV disease are previously healthy, young infants. During the 1995–1996 respiratory virus season, 69% of 95 children hospitalized at the New England Medical Center with RSV infection were full-term infants with normal cardiac and pulmonary status. Therefore, use of RSV-IGIV in appropriately selected, high-risk infants is unlikely to dramatically reduce the overall number of RSV induced admissions. However, high-risk children have a disproportionately high economic impact on RSV-associated health care costs because of the greater disease severity and the complexity of care required for these groups. In appropriately selected infants for whom the risk of hospitalization due to RSV and other respiratory viruses is greatest, passive immunoprophylaxis should have an important medical impact and improve their quality of life.

BackgroundRespiratory syncytial virus (RSV) vaccines were approved in 2023 and recommended for adults over the age of 75 and adults aged 60 – 74 at high risk of severe RSV infection. In this study, we investigated nationwide RSV vaccine administration and the efficacy of RSV vaccines in adults aged over 60.Figure 1.Monthly RSV vaccinations and testing volumes in adults 60 - 74 years of age and in adults 75+ from September 2022 to December 2024. Gray bars and the left y-axis indicate RSV testing volumes. Orange bars and right y-axis indicate RSV vaccination volumes.Figure 2.RSV testing volumes normalized to all respiratory panel testing volumes in December of 2022 – 2024 in adults 60 – 74 years of age and in adults 75+MethodsWe conducted an observational analysis of two nationwide, deidentified crossover datasets of 107,035 RSV vaccination events from September 2023 to December 2024 and 6,660 RSV diagnostic testing from September 2022 to December 2024 in adults over the age of 60 who were administered seasonal vaccinations. Time-to-event analysis was conducted for 110 adults over age 60 with RSV diagnostic testing performed at Labcorp within one year of vaccination.Figure 3.Monthly RSV positivity rates and vaccination volumes in adults 60 – 74 years of age and in adults 75+ from September 2022 to December 2024. Line plot indicates RSV positivity rates. Orange bars and right y-axis indicate RSV vaccination volumes. Shapes indicate the number of diagnostic tests performed per month.Figure 4.RSV diagnostic testing results within one year of RSV vaccination in 57 adults o60 – 74 years of age and in 53 adults 75+. Bars are colored by when each patient received the RSV vaccine.ResultsPeak uptake of RSV vaccines occurred in November 2023 in the 2023 – 2024 RSV vaccination season and in October 2024 in the 2024 – 2025 RSV vaccination season in adults aged 60 – 74. For adults 75+, peak vaccine uptake occurred in November 2023 and October 2024 (Fig 1). Peak RSV testing in adults aged 60 – 74 occurred in December. Peak RSV testing in adults 75+ occurred in December 2022 and in January and December 2024. Peak uptake of RSV vaccines occurred 1 – 2 months prior to the peak RSV testing months. Testing volumes in peak testing month of December decreased by 43.8% in adults aged 60 – 74 and by 42.5% in adults 75+ 2024 from 2023 (Fig 2). Peak RSV positivity rates in 2023 – 2024 RSV vaccination season occurred in December in adults aged 60 – 74 (9.3%) and adults aged 75+ (7.4%; Fig 3). Vaccine uptake peaked 1 – 2 months prior to peak RSV positive months. There were no breakthrough RSV infections in 57 adults aged 60 – 74 or in 53 adults aged 75+ with RSV diagnostic testing within one year of vaccination (Fig 4).ConclusionOur data demonstrate a potential correlation between the introduction of RSV vaccines and a reduction in RSV diagnostic testing in older adults. Furthermore, our data suggests that RSV vaccination is highly protective for RSV infection with zero breakthrough infections in a limited dataset. Further longitudinal study is warranted.DisclosuresKathryn Lang, MD, PhD, VaxCare: Advisor/Consultant David Alfego, PhD, Labcorp: Employee|Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company) Min Kyung Lee, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company) Laura Gillim, PhD, Labcorp: Stocks/Bonds (Public Company) Charles M. Walworth, MD, Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company)|Labcorp: Stocks/Bonds (Public Company) Suzanne Dale, PhD, Labcorp: Stocks/Bonds (Public Company) Colm Smart, MBA, VaXcare: Stocks/Bonds (Private Company) Ruth Carrico, PhD, DNP, APRN, VaxCare: Advisor/Consultant Payman Ghasemi, PhD, VaxCare: Grant/Research Support

Older adults and adults with certain chronic conditions are at increased risk for severe respiratory syncytial virus (RSV) disease. In 2023, RSV vaccines first became available in the United States (US) for adults aged ≥60 years. This retrospective database analysis evaluated RSV vaccination uptake from August 2023–February 2025 using IQVIA’s open-source pharmacy (LRx) and medical (Dx) claims data. The study included US adults aged ≥60 years with ≥1 claim in 2023. For those without RSV vaccination in 2023, ≥1 claim was also required between January 2024–February 2025. Uptake was assessed as the number and percentage of eligible adults who received an RSV vaccine during the study period. Multivariable logistic regression modeling explored factors associated with RSV vaccination. Nearly 12.8 million adults aged ≥60 years (16.4%) received RSV vaccination between August 2023–February 2025. Uptake generally increased with age and was higher among those with ≥1 potential risk factor for severe RSV disease. Disparities in uptake were observed by race, ethnicity, and other social determinants of health. In multivariable analyses, odds of RSV vaccination were nearly 24 times higher for those who received ≥1 non-RSV vaccine from August 2023–February 2025 versus those who had not. Despite the increased risk of severe RSV disease among older adults and those with certain risk factors, relatively limited RSV vaccination uptake was observed during the 2023–2025 seasons, with disparities observed. Additional efforts are needed to support RSV prevention among those at highest risk and to ensure equitable access to vaccination.

In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts. To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines. During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional study from 26 hospitals in 20 US states. Sociodemographic and clinical data were abstracted from health records, and structured interviews were conducted for knowledge and attitudes about RSV disease and RSV vaccines. Age, sex, race and ethnicity, pulmonary disease, immunocompromised status, long-term care facility residence, medical insurance, social vulnerability index (SVI), and educational level. The exposures were identified a priori as possible factors associated with RSV vaccine receipt and were entered into a modified Poisson regression model accounting for state clustering, to assess for association with RSV vaccine receipt. Knowledge and attitudes were summarized with frequencies and proportions. Among 6746 hospitalized adults 60 years or older, median age was 73 (IQR, 66-80) years and 3451 (51.2%) were female. Among the 6599 patients with self-reported race and ethnicity, 699 (10.6%) were Hispanic, 1288 (19.5%) were non-Hispanic Black, 4299 (65.1%) were non-Hispanic White, and 313 (4.7%) were other race or ethnicity. There were 700 RSV-vaccinated (10.4%) and 6046 unvaccinated (89.6%) adults. Among 3219 unvaccinated adults who responded to RSV knowledge questions, 1519 (47.2%) had not heard of RSV or were unsure; 2525 of 3218 (78.5%) were unsure if they were eligible for RSV vaccine or thought they were not. In adjusted analyses, characteristics associated with RSV vaccination were being 75 years or older (adjusted risk ratio [ARR], 1.23; 95% CI, 1.10-1.38, P < .001), being male (ARR, 1.15; 95% CI, 1.01-1.30; P = .04), and having pulmonary disease (ARR, 1.39; 95% CI, 1.16-1.67; P < .001), immunocompromised status (ARR, 1.30; 95% CI, 1.14-1.48; P < .001), low (ARR, 1.47; 95% CI, 1.18-1.83, P < .001) or moderate (ARR, 1.47; 95% CI, 1.21-1.79; P < .001) SVI, and educational level consisting of 4 or more years of college (ARR, 2.91; 95% CI, 2.14-3.96; P < .001), at least some college or technical training (ARR, 1.85; 95% CI, 1.35-2.53; P < .001), or grade 12 education or General Educational Development (ARR, 1.44; 95% CI, 1.03-2.00; P = .03). RSV vaccination was less likely among residents of long-term care facilities, patients with Medicaid coverage, and uninsured patients. In this cross-sectional study of hospitalized adults, knowledge of RSV disease and RSV vaccine eligibility was low. Older adults and those with certain medical conditions were more likely to have received vaccine, suggesting appropriate prioritization, but sociodemographic differences in vaccine uptake occurred.

Globally, it is estimated that respiratory syncytial virus (RSV) causes 33 million new episodes of acute lower respiratory tract infection (LRTI) in children <5 years of age and ≈120,000 deaths annually. In infants, RSV represents the leading cause of hospitalization worldwide and the second commonest cause of mortality in low- and middle-income countries.1,2 RSV also causes significant disease in immunocompromised hosts and the elderly and has been associated with the development of asthma.3 The increasingly recognized burden of RSV disease has made the development of a vaccine(s) a global health priority. The World Health Organization recently released a roadmap to facilitate the development and implementation of vaccines and monoclonal antibodies (mAbs) and estimated that RSV vaccination will be available in the next 5–10 years.4 This review summarizes the strategies and challenges associated with RSV vaccine development and the vaccine candidates undergoing clinical evaluation, with a focus on those geared toward the pediatric population. THE STRUCTURE OF RSV RSV has a negative sense nonsegmented RNA genome that encodes 11 proteins: 3 are nonstructural (NS1/NS2—that counteract interferon responses—and M2-2), and 8 are structural proteins. Of those 8 proteins, 5 are internal [N, P, M, M2-1, L]), and 3 are embedded in the virion membrane: the small hydrophobic (SH), fusion (F) and attachment (G) glycoproteins. RSV G and F carry antigenic determinants that elicit neutralizing antibodies. However, F is the preferred target for vaccine, mAb and antiviral development because it plays an essential role in host cell viral entry, is highly conserved within and among RSV A and B subtypes and because of its 6 antigenic sites that elicit the production of high-potency neutralizing antibodies (≥90% of neutralizing antibodies are directed against this protein).5 Most of the G protein is covered in glycans, leaving the central conserved domain available for neutralizing antibody binding. Except for this domain, G is not well conserved and it is recognized by few neutralizing antibodies, which has reduced enthusiasm for it as a vaccine target. Our understanding of the F protein in its 2 conformations, prefusion (pre-F) and postfusion (post-F), has revolutionized the field of RSV biology. Pre-F, the active form of F on the virion, is metastable and switches unpredictably to the stable post-F conformation that once it is folded cannot return to the pre-F form. Antibodies that bind to pre-F are more efficient at neutralizing RSV than those against post-F. As examples, antibodies against site ϕ, a pre-F-specific epitope, are 150 times more potent than palivizumab that binds to site-II, present in both F conformations, while antibodies against site I, exclusively present in post-F, show weak or no neutralization.5 In addition, non-neutralizing antibodies to F, G and also SH, may inhibit infection by complement-mediated neutralization or antibody-dependent cell-mediated cytotoxicity. Furthermore, all viral antigens have the potential to induce protection by T-cell-mediated immunity. CHALLENGES FOR RSV VACCINE DEVELOPMENT Despite the burden associated with RSV, and after 60 years of active research, there is no licensed vaccine due in part of our incomplete understanding of the pathogenesis of the disease. In general, primary RSV infections are more severe; however, reinfections are common throughout life as immunity is neither complete nor long-lasting. The ideal vaccine should induce a more durable and improved immune response than natural infection. Legacy of the Formalin-inactivated Vaccine RSV vaccine development has been hindered after the safety concerns of the first RSV vaccine that was developed in the 1960s. The formalin-inactivated-whole virus alum-precipitated vaccine, which recent evidence indicating that it was directed against post-F, was associated in naive infants, but not older children, with enhanced RSV disease (ERD) and 2 deaths upon subsequent exposure to natural RSV. The mechanisms of ERD are not well understood, but it appears that an excess of non-neutralizing antibodies coupled with a skewed T-helper 2 (Th2) immune response, and complement deposition in the lungs contributed to its development. This is a critical aspect that is being considered for the development of inactivated vaccines, and strategies to assess safety risks according to the different vaccine platforms in the infant population are required. Target Populations There are different age groups that will benefit from RSV vaccines, and these might require different approaches: young RSV-naive infants (<4–6 months), children >6 months and the elderly. Vaccination of older children (2–5 years of age) may also limit transmission, as older siblings frequently introduce RSV into the household. Infants <4–6 Months This age group has an immature/developing immune system characterized by low expression of interferon, abundance of regulatory T cells with tolerogenic reactivity and a limited B-cell repertoire because of inefficient generation of somatic hypermutations. All these factors are associated with a poor response to foreign antigens and the generation of high-affinity matured antibodies. In addition, the presence of maternal antibodies may interfere with vaccine immunogenicity. Young infants represent the main target population because the peak of severe RSV disease occurs in the first 2–3 months of life. This age group would likely benefit from maternal vaccination or neutralizing mAbs administered at birth. The main goal of maternal vaccination is to boost neutralizing RSV titers and thereby transplacental antibody transfer. However, the optimal timing for vaccination (2nd or 3rd trimester) and the durability of protection in the infant need to be defined. This coupled with the high prevalence of hypergammaglobulinemia in low- and middle-income countries, associated with HIV or malaria, which impairs transplacental antibody transfer, suggest the need for high maternal antibody titers to compete for transfer. Nevertheless, RSV antibody transfer through breast-feeding (IgG > IgA) may complement the maternal vaccination strategy.6 Vaccinating pregnant women could be questioned if it exclusively benefits the infant and not the mother. The limited data available in pregnant women are mostly derived from influenza surveillance studies with rates of RSV infection varying from 0.2% to 13%, which likely underestimates the real incidence of RSV during pregnancy. The concerns regarding adverse fetal outcomes are relatively low, because this would not be the first time the mother's immune system encounters RSV antigens and the safety profile of other vaccines used in pregnancy, such as tetanus, diptheria and acellular pertussis (Tdap) or influenza, is excellent. A number of RSV maternal vaccines are currently in clinical development (Table 1).TABLE 1.: Landscape of RSV Vaccines Undergoing Clinical TrialsOlder Infants and Children Based on the experience of the formalin-inactivated-RSV vaccine, within this age group those who are naive at the time of vaccination might be at risk of ERD with protein vaccines. This target population would likely benefit most from live-attenuated or vectored vaccines. The Elderly On the other side of the spectrum, the immunosenescence of adults >65 years of age and the presence of additional comorbidities may compromise vaccine responses and the ability to assess efficacy. This population might benefit most from adjuvanted vaccines. Clinical Endpoints The ideal vaccine should be able to prevent severe disease and limit transmission, but the lack of a standard definition of severe disease or precise markers to assess severity in infants has been a barrier for vaccine development. Clinical endpoints that define a successful vaccine might be different depending on the target population. Hospitalization and other endpoints that capture the inpatient/outpatient burden of the disease, such as a reduction in medically significant visits for RSV infection, should be considered.7 Developing composite endpoints that include a combination of viral (and possibly bacterial) factors, clinical parameters, and fast turn-around point of care biomarkers could help with patient classification and to standardize definitions.8 Also, long-term follow-up is recommended, as studies suggest that interventions reducing the acute burden of RSV disease may also impact the development of recurrent wheezing/asthma.9 Immune Correlates of Protection Serum neutralizing antibodies (IgG against pre-F > post-F and G) represent the main surrogate of protection, as shown by the effectiveness of immunoprophylaxis with anti-F mAb (palivizumab) in high risk infants. However, a standardized protective threshold has not been defined yet. Newer systems biology approaches are helping to define the optimal correlates of protection, which are complex and depend on multiple factors, rather than a single cutoff value in antibody assays, and will need to be adjusted to each target population. Other cocorrelates of protection may include, F-specific epitope antibodies, mucosal IgA, interferon responses, antibody-dependent cell-mediated cytotoxicity and cell-mediated immunity. In addition, a balanced Th1/Th2 immune response, indicated by a high IgG2a/IgG1 ratio, is desirable. Other Factors The lack of an ideal animal model has also slowed down RSV vaccine development. Human challenge models mostly reproduce upper but not LRTI, limiting the generalizability of the results or the ability to assess the impact of vaccines on disease severity. There are also gaps in RSV epidemiology with lack of accurate information defining the temporal and geographic patterns of RSV circulation in inpatients/outpatients, across different age groups or RSV-associated mortality. Implementing robust multiplex polymerase chain reaction-based surveillance platforms could help to assess the impact of interventions on the burden of RSV disease, to identify possible escape mutants, or the contribution of other respiratory viruses causing RSV-like illnesses. VACCINE STRATEGIES The most effective approach to protect young infants and children from severe RSV infection may be a combined strategy using passive and active immunization: either maternal vaccination with stabilized pre-F or virus-like particles containing the F protein or mAb against pre-F at birth; followed by pediatric active immunization with a live vaccine, either attenuated RSV or the pre-F protein expressed from a virus vector. There are 39 vaccines candidates under development (http://www.path.org); of those 19 are undergoing clinical trials (Table 1).10 Protein Vaccines Particle Based The recombinant adjuvanted RSV post-F nanoparticle vaccine is the most advanced vaccine in clinical development. Results from a phase-3 clinical trial that enrolled 4636 pregnant women on the third trimester demonstrated a decrease in RSV hospitalizations in the offspring; however, the study did not meet the primary endpoint defined as prevention of medically significant RSV LRTI. The potential approval of this vaccine is being evaluated. It also aims to target elderly individuals and children >6 months to 5 years of age. Subunit Vaccines These vaccines consist of purified, adjuvanted proteins and use stabilized pre-F as the main antigen with promising results. They are mainly directed at pregnant women or the elderly because of the risk of ERD in RSV-naive infants. Other subunit vaccines in clinical or preclinical stages are using SH or G as main vaccine antigens. Live Vaccines Vector Based There are 5 vector-based vaccines in clinical development. The first 4 use adenovirus as a vector, while the other uses a modified vaccinia Ankara virus. Two of them are intended for use in pediatric seronegative patients. All of these vaccines express RSV F (pre-F > post-F depending on the vaccine) and 2 of them also express other viral antigens (N, M2 or G proteins). Live-attenuated vaccines (LAVs) represent an attractive alternative for older infants and young children. LAVs are administered intranasally and are able to elicit broad innate, humoral and cellular responses and replicate in the respiratory tract despite the presence of maternal antibodies. Importantly, these vaccines have not been associated with ERD and are considered safer in infants. The use of reverse genetics has made possible to incorporate different mutations in the viral genome, making LAV sufficiently immunogenic and, except for rhinorrhea, not associated with adverse events. There are 6 intranasal LAVs undergoing phase-1 clinical trials; 4 are using attenuated RSV, one Sendai virus as a backbone expressing RSV F and the last one is a chimeric vaccine using bacille Calmette-Guerin (BCG). The BCG/RSV vaccine is the only LAV intended to be administered systemically (subdermal) and in newborns. MONOCLONAL ANTIBODIES mAbs are also being evaluated for the prevention of RSV LRTI in young infants. Of those, suptavumab (REGN-2222), that targeted the pre-F-specific site V, has been discontinued from the market after it failed to prevent serious RSV LRTI in premature infants (primary endpoint). During the study, RSV type B was the predominant circulating strain and developed escape mutations that conferred resistance to this mAb. MK-1654 is an extended half-life mAb currently undergoing phase-I clinical trials and it is directed against antigenic site-IV (present the pre-F and post-F forms). Nirsevimab (MEDI8897) is a highly potent human neutralizing IgG1Κ targeting the pre-F-specific antigenic site ϕ. It also has an extended half-life because of modifications in the FC region using YTE technology. MEDI8897 is entering phase-3 clinical trials with the intent to provide passive immunization for prevention of severe RSV LRTI to all infants (preterm and full term), using a fixed, once per season intramuscular dose. SUMMARY Over the past decade, there have been significant advances in our knowledge of RSV molecular and structural biology and in the understanding of the human immune response to RSV. Despite the barriers, there are several opportunities for RSV vaccine development to protect the most vulnerable populations. The increasing interest of academic, industry and international bodies, such as the World Health Organization or Bill & Melinda Gates Foundation, is helping to move the field forward, promoting the implementation of surveillance platforms and standardization of clinical definitions, assays and surrogate markers of protection.

The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.

Background In 2023, two respiratory syncytial virus (RSV) vaccines became available in the United States (US) for adults aged ≥60 years and were recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices using shared clinical decision-making (i.e., requiring joint decision-making between healthcare professionals and their patients). This study evaluated RSV vaccination uptake through February 2024, overall and by specific risk factors for severe RSV disease.Figure 1.Age-specific RSV vaccination uptake among US adults aged ≥60 yearsRSV = respiratory syncytial virus; US = United States. Note: Patients with data quality issues or who received an RSV vaccine before August 1, 2023 were excluded from analyses. Methods A retrospective database analysis evaluated RSV vaccination uptake between August 1, 2023-February 29, 2024, using IQVIA’s open-source pharmacy (LRx) and medical (Dx) claims data. The study included patients aged ≥60 years who had ≥1 claim between January 1, 2023-February 29, 2024. Monthly and cumulative uptake were assessed as the number and percentage of eligible older adults who received an RSV vaccine during the study period, with cumulative uptake stratified by potential risk factors for severe RSV disease (e.g., chronic pulmonary or cardiovascular conditions). Descriptive analyses were based on observed vaccination claims (data were not projected to US population).Figure 2.RSV vaccination uptake among US adults aged ≥60 years, by potential risk factors for severe RSV diseaseCAD = coronary artery disease; CCI = Charlson Comorbidity Index; COPD = chronic obstructive pulmonary disease; RSV = respiratory syncytial virus; US = United States. Note: Patients with data quality issues or who received an RSV vaccine before August 1, 2023 were excluded from analyses. Potential risk factors for severe RSV disease were identified based on the presence of relevant diagnosis and/or procedure codes in claims prior to August 1, 2023 (i.e., using all available history). For the analysis by frailty status, patients were required to have claim activity (both medical [Dx] and pharmacy [LRx]) and stability during the 1-year period prior to August 1, 2023. Frailty status was evaluated based on the presence of a diagnosis for age-related physical debility and/or cumulative frailty score ≥2 based on age and CCI score (using all available history). For age, patients received a score of 0 if aged ≤75 years, 1 if aged 76-80 years, and 2 if aged ≥81 years. For CCI, patients received a score of 0 if CCI ≤1 and 1 if CCI ≥2. Results Nearly 9.2 million older adults (10.0%) received an RSV vaccination between August 2023-February 2024, with 26.1% of vaccinations occurring in October. Cumulative uptake by age was lowest among adults aged 60-64 years (4.7%) and highest among adults aged 75-79 years (14.0%) (Figure 1). RSV vaccination uptake was higher among older adults with ≥1 potential risk factor for severe RSV disease (11.5%) versus those without any risk factors (7.9%). Among evaluated risk factors, uptake ranged from a low of 7.7% for older adults with dementia to a high of 15.9% for frail older adults (Figure 2). Conclusion Approximately 1 in 10 adults aged ≥60 years received an RSV vaccination during the first season of vaccine availability, with relatively low uptake observed across ages and evaluated risk factors. Previous research has estimated that nearly half of older adults have a diagnosed risk factor for severe RSV disease, suggesting that additional efforts are needed to support RSV prevention among older adults at highest risk. FUNDING: GSK (GSK study identifier: VEO-000828) Disclosures Elizabeth M. La, PhD, GSK: employee|GSK: Stocks/Bonds (Private Company) Catherine B. McGuiness, MA, MS, GSK: Advisor/Consultant David Singer, PharmD, MS, GSK: employee|GSK: Stocks/Bonds (Public Company) Marie Yasuda, PharmD, MS, Amgen: Grant/Research Support|Bayer: Grant/Research Support|BMS: Grant/Research Support|GSK: Advisor/Consultant|Novartis: Grant/Research Support|Sandoz: Grant/Research Support|Servier: Grant/Research Support Chi-Chang Chen, PhD, MSPharm, Amgen: Grant/Research Support|Bayer: Grant/Research Support|BMS: Grant/Research Support|GSK: Advisor/Consultant|Novartis: Grant/Research Support|Regeneron: Grant/Research Support

Background During the 2024–2025 respiratory syncytial virus (RSV) season in the United States (US), RSV vaccination was recommended by the Advisory Committee on Immunization Practices (ACIP) for all adults aged ≥ 75 years and adults aged 60–74 years at increased risk for severe RSV disease. This study evaluated RSV-related knowledge, attitudes, and practices (KAP) among US healthcare professionals (HCPs), including primary care physicians (PCPs) and specialist physicians. Methods A cross-sectional online survey of RSV-related KAP was administered to US HCPs between December 2024–January 2025. The survey targeted 700 HCPs, including PCPs (n=200), specialists (n=150), nurse practitioners and physician assistants (n=150), and pharmacists (n=200). Descriptive results are presented here on PCPs’ and specialists’ knowledge of adult RSV disease and vaccination, RSV-related attitudes, RSV vaccination practices, and potential vaccination barriers. Results The final sample of 700 HCPs included 199 PCPs and 153 specialists (50 cardiologists, 50 endocrinologists, and 53 pulmonologists). Most PCP and specialist respondents reported being very familiar with RSV disease (83.9% and 80.4%, respectively). At the time of data collection, 81.3% of PCPs and 75.0% of specialists were aware that RSV vaccines were ACIP-recommended among all adults aged ≥ 75 years. However, fewer respondents were aware of the risk-based ACIP recommendation for adults aged 60–74 years (32.8% of PCPs and 27.0% of specialists). Most respondents perceived a benefit of having RSV vaccines available and recommended for all adults aged 60–74 years. Although more than 80% of PCPs and specialists reported recommending RSV vaccines to their eligible patients, these recommendations were not provided to all eligible patients consistently. Patient refusal or hesitancy was the most frequently reported barrier to recommending RSV vaccination to adults aged ≥ 60 years. Conclusion Despite the familiarity of RSV disease among PCPs and specialists, additional efforts may be needed to address potential knowledge and practice gaps. These findings can help to inform HCP and patient education to support RSV vaccination among eligible patients. Funding: GSK VEO-001082 Disclosures Elizabeth M. La, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Kyli Gallington, MPH, Evidera: Employed by Evidera|GSK: Employed by Evidera, which received funding from GSK to conduct this study David Singer, PharmD, MS, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Zaneta Balantac, ScB, Evidera: Employed by Evidera at the time of this study|GSK: Formerly employed by Evidera, which received funding from GSK to conduct this study Noha S. Eltoukhy, PharmD, MPH, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Yipin Han, MHS, Evidera: Employed by Evidera|GSK: Employed by Evidera, which received funding from GSK to conduct this study Donald M. Bushnell, MA, Evidera: Employed by Evidera|GSK: Employed by Evidera, which received funding from GSK to conduct this study

Background The new and effective RSV vaccine can reduce morbidity from RSV among older adults, yet uptake is below goal and there are differences in uptake across race/ethnicity and income groups. Thus, we sought to describe barriers and facilitators to RSV vaccine uptake among Latino older adults and likelihood of recommending the vaccine to their family members.Demographics of Survey ParticipantsBehavioral and Social Determinants of RSV Vaccination Among adults 60+ years Methods In this cross-sectional study, we administered surveys to a convenience sample of adults at Latino-focused community-based organizations and churches. Surveys assessed barriers and facilitators of RSV vaccination using Behavioral and Social Drivers (BeSD) conceptual model (Figure 1). We assessed sociodemographic variables and the odds of being motivated to get the RSV vaccine (60+ years) with a logistic regression, adjusting by age, sex, and race.Predictors of Intention to Vaccinate (BeSD Domain: Motivation) and Confidence in Vaccine Benefits (BeSD Confidence) Among Adults 60 Years of Age and OlderBehavioral and Social Drivers of Vaccination Results From November 2024 to February 2025, we administered 403 surveys (200 among adults 60+). Majority of participants were Latino (87%) and born outside of the US (87%) (Table 1). Among adults 60+, 3% received the RSV vaccine, whereas 47% received the zoster vaccine and 82% received a COVID booster. Prior to the survey, 58% had never heard of the RSV virus. Once made aware of RSV and vaccine eligibility, 67% were motivated to get vaccinated and 68% felt the vaccine was very important (Table 2). Confidence in vaccine benefits was highly correlated with motivation, with 71% of people who felt the vaccine was important expressing strong motivation to get the vaccine. After adjusting for age, sex, and race, older adults’ motivation to get the RSV vaccine was positively associated with confidence in vaccine safety (aOR: 9.8, 95%CI: 3.2-30.2), trust in health workers (aOR: 5.1, 95%CI: 1.7-15), and social norms-- family and friends want them to get vaccine (aOR: 5.3, 95%CI: 2.5-11) (Table 3). Practical challenges were reported, with 73% expressing cost concerns. Among people 18-59 years, 77% discuss health matters with their older family members and 70% would recommend the RSV vaccine. Conclusion After hearing about RSV vaccine eligibility, motivation to get vaccinated was high, though actual vaccine uptake was only 3%. Strategies to increase uptake should include education from trusted sources including health care providers, family members and friends about vaccine eligibility and access. Disclosures Diane Havlir, MD, VIiV: Grant/Research Support

BackgroundSince June 2024, CDC’s Advisory Committee on Immunization Practices (ACIP) has recommended a single dose of RSV vaccination for all adults aged ≥75 years and for adults aged 60–74 years who are at increased risk of severe RSV disease. RSV vaccines are effective in preventing RSV-associated hospitalization, with the potential to prevent tens of thousands of annual hospitalizations and deaths in older adults. However, certain adults aged < 60 years are also at increased risk of severe illness caused by RSV.MethodsIn considering RSV vaccination for adults aged 50–59 years, ACIP reviewed risk of RSV-associated hospitalization among adults with and without chronic medical conditions, differential risk by race and ethnicity, duration of vaccine protection and potential need for revaccination, risk of Guillain-Barre syndrome (GBS) associated with subunit RSV vaccines, national vaccine uptake, societal costs of the vaccination program, complexity of changes to the immunization schedule, and challenges in implementing a risk-based recommendation in retail pharmacies, where most older adults have received RSV vaccination.ResultsACIP members discussed variability in individual-level risk of severe RSV disease in persons with specific chronic conditions and the balance of benefits and risks of RSV vaccination in adults aged < 60 years, who generally experience lower risk of severe outcomes from RSV infection compared with older adults. Members were concerned about the disproportionate burden of severe RSV disease and higher prevalence of chronic medical conditions among Black adults in the U.S., particularly in the 50–59-year age group. Members expressed a need for more data to inform optimal timing of revaccination after vaccine-induced immunity wanes, which is particularly important for younger adults with longer remaining life expectancy.ConclusionOverall, Committee members thought that the public health benefits of RSV vaccination outweighed risks for adults aged 50–59 years with certain chronic medical conditions. On April 16, 2025, ACIP recommended a single dose of RSV vaccine for these adults using the same qualifying risk conditions used for adults aged 60–74 years. ACIP plans to consider RSV vaccine recommendations for adults aged 18–49 years at a future public meeting.DisclosuresHelen Y. Chu, MD, MPH, Roche: Advisor/Consultant|Vir: Advisor/Consultant

BackgroundOn June 26, 2024, the CDC updated respiratory syncytial virus (RSV) vaccine recommendations to a single dose of RSV vaccine for all adults aged ≥ 75 years and adults aged 60-74 years with increased risk of severe RSV disease. Using electronic health record (EHR) data from the VISION platform, we described characteristics of patients testing negative for RSV who did and did not receive an RSV vaccine and assessed factors associated with RSV vaccine receipt.Figure 1:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccination among test-negative patients with an emergency department (ED) encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=23,403 patientsFigure 2:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccine among test-negative patients with an inpatient encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=25,020 patientsMethodsPatients with ≥ 1 emergency department (ED) or inpatient encounter at any of 6 participating health systems in 8 states with RSV-like illness (RLI) during October 1, 2024-March 31, 2025 were included. Vaccination status was ascertained from EHR, state and city immunization information systems, and medical claims. Patients who tested positive for SARS-CoV-2 or influenza viruses at the same RLI encounter were excluded. Patient age, sex, race and ethnicity, Medicaid status, number of underlying medical conditions, month of medical encounter, and documented receipt of COVID-19 or influenza vaccines were evaluated as covariates when assessing the odds of vaccination. The best fitting multivariable logistic regression models using Bayesian Information Criterion were chosen.ResultsAmong 48423 included patients, 2113 (4.4%) had documented RSV vaccine receipt. The odds of RSV vaccination differed by site and increased with calendar time and age. Compared to patients aged 60-64 years, those aged ≥ 75 years were more likely to have received an RSV vaccine (ED: aOR: 3.6, 95%CI: 2.7-4.8, Figure 1; inpatient: aOR: 2.3, 95%CI: 1.7-3.0, Figure 2). Receipt of both influenza and COVID-19 vaccine within the same season had the strongest association with RSV vaccination in both the ED (aOR: 14.88, 95%CI: 11.87-18.89, Figure 1) and hospital setting (aOR: 20.04, 95%CI: 16.20-25.03, Figure 2).ConclusionReceipt of other respiratory viral vaccines was the strongest indicator of RSV vaccination in the 2024-2025 RSV season in patients testing negative for RSV among all demographic and clinical characteristics considered. RSV vaccination was lower among those aged 60-64 years than older patients. These findings inform future methods to estimate vaccine effectiveness and inform policy implementation.DisclosuresGabriela Vazquez-Benitez, PhD, MSc, AbbVie: research funding not related to this study|Sanofi: Grant funding for other research not related to this study Stephanie Irving, MHS, Westat: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Jingran Cao, MS, Sanofi Pasteur: Grant/Research Support Charlene E. McEvoy, MD, MPH, Astra Zeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|Department of Defense: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|National Institutes of Health: Grant/Research Support|PCORI: Grant/Research Support Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support John R. Hansen, MPH, Centers for Disease Control and Prevention: Grant/Research Support Lawrence Block, MPH, MPA, Centers for Disease Control and Prevention: Grant/Research Support Karen B. Jacobson, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research Support Catia Chavez, MPH, Westat: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

Background and Objectives: Three respiratory syncytial virus (RSV) vaccines have been recently made available for older adults. Understanding the principal characteristics of the first vaccine-takers can pave the way for a successful vaccination campaign. The objective of this study was to explore the sociodemographic and clinical characteristics of the first Italian users of an adjuvanted RSV vaccine and their attitudes towards RSV and vaccination. Materials and Methods: This cross-sectional study was conducted in 2024 in Liguria (Italy). Individuals aged ≥60 years with no contraindications to the adjuvanted vaccine RSVPreF3 OA were eligible. Following vaccination, subjects filled in a questionnaire, which comprised items on sociodemographic and clinical characteristics, attitudes towards RSV and RSV vaccination and a vaccination trust indicator (VTI). Results: A total of 453 vaccinees completed the survey. Their mean age was 74.9 ± 8.0 years, and 50.6% were males. Nine of ten (89.2%) individuals had ≥1 co-morbidity, of which cardiovascular conditions (70.4%), respiratory diseases (27.6%) and diabetes (18.5%) were the most common. Uptake of the routine vaccines was high: 91.2% and 98.7% received the 2023/2024 season influenza and ≥2 COVID-19 vaccines, respectively. The most common reasons for the current RSV vaccination were general practitioner advice (43.9%), followed by the willingness to be protected against (20.8%) and feelings of being at risk (16.6%) of RSV. The average VTI score was 91.5%, suggesting high trust in vaccines. More positive attitudes towards RSV vaccination were observed (p < 0.01) among subjects who received more COVID-19 vaccine doses, whose reasons for the current RSV vaccination were the willingness to be protected or to be in good health and the feeling of being at risk for RSV. Conclusions: The first Italian users of the novel RSVPreF3 OA vaccine were represented by high-risk individuals with a comparatively high prevalence of co-morbidities, high uptake of the seasonal respiratory vaccines and high trust in immunization.