A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses

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

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.

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

To investigate respiratory syncytial virus (RSV) vaccine uptake, associations, and breakthrough infection among patients with systemic autoimmune rheumatic diseases (SARDs). We performed a retrospective cohort study investigating RSV vaccination among patients with SARDs at Mass General Brigham (Boston, Massachusetts, USA). We identified all patients with SARDs who were aged ≥ 60 years and thus eligible to receive the RSV vaccine between May 2023 and February 2025. We used multivariable logistic regression to identify factors associated with RSV vaccination. Among the vaccinated, we described documented cases of laboratory-confirmed breakthrough RSV infection. Among 10,587 patients with SARDs (median age 71.7 years, 72.4% female) eligible for RSV vaccination, 1075 (10.2%) received RSV vaccination. Factors associated with higher odds of RSV vaccination included higher median census-tract household income and comorbidities, such as cancer and interstitial lung disease. Associations with lower odds of RSV vaccination included Black race, lack of previous influenza or COVID-19 vaccinations, and glucocorticoid use. RSV vaccination was not associated with specific SARD types or disease-modifying antirheumatic drugs (DMARDs), including CD20 inhibitors. Among the 1075 who were vaccinated, there were 9 (0.8%) documented cases of RSV breakthrough infection (2 hospitalizations and no deaths). CONCLUSION: Only 10.2% of eligible patients with SARDs received RSV vaccination. Glucocorticoid users were less likely to receive RSV vaccination, whereas specific SARD types and DMARDs were not associated. Although some predictors of vaccine uptake were observed in this dataset, there are many unmeasured factors that may play a role in vaccine uptake. There were few documented breakthrough infections and no deaths. Future studies are needed to optimize RSV vaccine use and establish safety and efficacy in this vulnerable population.

Quantifying the prevalence and determinants of respiratory syncytial virus (RSV) vaccine hesitancy in US adults aged 60 or older

Respiratory Syncytial Virus (RSV) vaccination was first approved by the Therapeutic Goods Administration of Australia for older adults in January 2024. We aimed to evaluate uptake among people aged ≥75years across different socioeconomic thresholds. Male and female FluTracking participants were included in this cross-sectional study if they had an Australian residential postcode documented, returned at least one weekly survey between 30 March 2025 and 2 December 2025 while aged ≥75years, and had a recently documented RSV, influenza, and COVID-19 vaccination status. Socioeconomic status (SES) was allocated by matching participant residential postcode to the Index of Relative Socio-economic Disadvantage for that postcode. Relative difference in vaccine uptake across SES categories was evaluated using logistic regression. A total of 10,376 participants were included (61.4% aged 75-79years, 54.2% female). High, medium, and low SES categories were represented by 5347 (51.5%), 3658 (35.3%), and 1371 (13.2%) participants, respectively. Recent RSV vaccination was reported by 19.6% of participants, recent influenza vaccination by 92.5%, and recent COVID-19 vaccination by 67.1%. In age, sex, and state/territory adjusted analyses, the odds of vaccination in the medium compared with the high SES group for RSV, influenza, and COVID-19 were 42.3%, 19.8%, and 24.0% lower, respectively. The adjusted odds of vaccination in the low SES group compared with the high SES group for RSV, influenza, and COVID-19 were 47.1%, 35.1%, and 30.2% lower, respectively. We found lower uptake of RSV vaccination among adults aged ≥75years compared with recent vaccination for influenza and COVID-19. Lower SES groups had lower uptake of all three vaccines compared with the high SES group and the relative difference in uptake across socioeconomic levels were more pronounced for RSV vaccination. Broad public funding for RSV vaccination among older adults in Australia could help to reduce inequity in uptake.

INTRODUCTION. Respiratory syncytial virus (RSV) is one of the most widespread pathogens that typically cause acute upper and lower respiratory tract infections in children and adults. Monoclonal antibody products have long been used for passive immunoprophylaxis in premature infants with bronchopulmonary dysplasia. However, vaccines have recently been licensed for the prophylactic immunisation of older adults with various risk factors for severe RSV infection (primarily, chronic cardiovascular and respiratory diseases and diabetes mellitus).AIM. This study aimed to review the current status of the development of vaccines for active immunisation against RSV infection, including the epidemiological rationale for their development, clinical trial results for licensed vaccines, recommendations for vaccination, and promising pipeline vaccines for RSV prevention.DISCUSSION. Initially hindered by the unique immunopathogenesis of RSV infection and the genetic hypervariability of RSV for a long time, attempts to develop an RSV vaccine succeeded when international researchers managed to identify a conservative neutralising antibody target capable of inducing specific immunity against RSV. This target, the RSV capsid protein stabilised in its prefusion (pre-F) conformation, can mediate viral entry into the cell following a conformational change. Several subunit vaccines based on recombinant pre-F proteins have successfully passed clinical trials and have been approved for the immunisation of older adults. In addition, one of these vaccines has been recommended for use during pregnancy to prevent RSV infection in newborns and infants. Currently, programmes are being implemented to develop novel RSV vaccines based on messenger RNA (mRNA) and non-replicating attenuated influenza vectors. This article examines and summarises the efficacy and safety parameters of two RSV vaccines approved in multiple countries around the world. Both vaccines have satisfactory safety profiles and comparable prophylactic efficacy parameters.CONCLUSIONS. Prelicensure clinical trials of novel RSV vaccines, including those being developed in the Russian Federation, should include prophylactic efficacy assessments in target patient populations. For vaccines approved by leading international regulators, clinical trials required for approval in the Russian Federation will be limited to bridging studies confirming the immunogenicity and safety of the vaccines.

Respiratory syncytial virus (RSV) vaccine effectiveness against RSV-associated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, October, 2023, to March, 2024: a test-negative design analysis

Respiratory syncytial virus (RSV) is the most important viral agent causing severe respiratory disease in infants and children. In temperate climates, RSV activity typically peaks during winter. We have described the seasonal variation in RSV activity and investigated which meteorological variables are related to RSV outbreaks for different time lags. Eleven laboratories in the Netherlands collected data on RSV during the period 1998-2005. Meteorological data were obtained from the Royal Netherlands Meteorological Institute. General linear methods were used to determine the relative contribution of meteorological conditions to reported RSV cases in the winter period. Time lags up to 4 weeks were included to assess a possible delayed weather effect in relation to RSV activity. Onset of RSV activity occurred around week 44 and activity peaked around week 52. Timing of peak activity was very consistent over the study period. Relative humidity was positively associated with RSV activity for all time lags, indicating more RSV when relative humidity increased. Minimum temperature was negatively associated with RSV activity and cloud cover was positively related with RSV activity. Interaction (P < 0.06) between minimum temperature and relative humidity was observed for a lag of 0, 1, and 2 weeks, indicating that the combination of low temperature and high humidity contributes more to RSV activity than temperature and humidity alone. Relative humidity, minimum temperature, and cloud cover are important predictors of RSV activity in the Netherlands, with the effect of relative humidity being most consistent.

Human respiratory syncytial virus (RSV) is a serious respiratory pathogen in infants and young children as well as elderly and immunocompromised populations. However, no RSV vaccines are available. We have explored the potential of virus-like particles (VLPs) as an RSV vaccine candidate. VLPs composed entirely of RSV proteins were produced at levels inadequate for their preparation as immunogens. However, VLPs composed of the Newcastle disease virus (NDV) nucleocapsid and membrane proteins and chimera proteins containing the ectodomains of RSV F and G proteins fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, were quantitatively prepared from avian cells. Immunization of mice with these VLPs, without adjuvant, stimulated robust, anti-RSV F and G protein antibody responses. IgG2a/IgG1 ratios were very high, suggesting predominantly T(H)1 responses. In contrast to infectious RSV immunization, neutralization antibody titers were robust and stable for 4 months. Immunization with a single dose of VLPs resulted in the complete protection of mice from RSV replication in lungs. Upon RSV intranasal challenge of VLP-immunized mice, no enhanced lung pathology was observed, in contrast to the pathology observed in mice immunized with formalin-inactivated RSV. These results suggest that these VLPs are effective RSV vaccines in mice, in contrast to other nonreplicating RSV vaccine candidates.

Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge

SummaryBackgroundThe first RSV vaccines for adults 60 years and older were approved prior to the 2023–2024 respiratory virus season. This study aims to evaluate RSV vaccine effectiveness (VE) in preventing RSV infections among older adults, and to examine antibody correlates of protection.MethodsThis study used data from adults 60 years and older, enrolled into the Community Vaccine Effectiveness (CoVE) prospective cohort study, in Michigan, U.S.A. A Cox regression model was used to compare incidence of symptomatic/all RSV infections in those vaccinated versus unvaccinated. RSV-specific (preF) binding antibodies were measured in serum specimens and assessed longitudinally. A correlates of protection analysis was conducted using logistic regression.FindingsOf the 281 participants (n = 117 vaccinated) enrolled (August 1, 2023, to March 1, 2024), 14 tested positive for RSV. Adjusted RSV VE against any RSV infection was 50.8% (95% CI: −79.1% to 86.5%), and 59.8% (95% CI: −105.2% to 92.1%) against symptomatic RSV. There were 61.2 (95% CI: 16.9, 163.2) RSV infections per 1000 person-years among participants who were vaccinated compared to 165.8 infections (95% CI: 88.0, 287.0) per 1000 person-years among those unvaccinated. A 31% decrease in odds (OR: 0.69, 95% CI: 0.44–1.07) of RSV infection per 2–fold increase in antibody concentration was observed.InterpretationOur findings suggest that higher antibody levels may be associated with a reduced risk of RSV infection, but further research is needed to confirm this relationship. RSV incidence appeared to be lowest among adults who were vaccinated, though the difference was not statistically significant. Low number of RSV events and limited availability of serology data limit the precision of the estimates. Continued monitoring of reduction of RSV infection in years following vaccination is warranted.Funding10.13039/100005224National Center for Immunisation and Respiratory Diseases, U.S. Centers for Disease Control and Prevention (75D30122C13149) and 10.13039/100000060National Institute of Allergy and Infectious Diseases (75N93021C00015). The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Respiratory syncytial virus (RSV) vaccination is recommended in pregnancy. Limited data exist regarding antibody (Ab) durability to inform revaccination timing. We conducted prospective cohort studies among pregnant and older adults after first RSV vaccination in 2023-2024. Longitudinal samples from 50 pregnant (36 vaccinated) and 16 vaccinated older adults were collected until 12-15 months after vaccination and tested for RSV binding and neutralizing Ab. Mean Ab levels 12-15 months after vaccination were similar between vaccinated maternal and older adult participants (P = .73), suggesting Ab durability up to 1 year after maternal RSV vaccination. RSV binding and neutralizing Ab titers were strongly correlated (R = .73).

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder that causes stiffness and pain in the proximal joints, including the shoulders, hips and neck. The exact cause of polymyalgia rheumatica is yet to be fully understood, but research suggests that both genetic and environmental factors may contribute to it. Studies have previously linked the onset and relapse of polymyalgia rheumatica symptoms to the influenza and COVID-19 vaccines. The Food and Drug Administration approved the respiratory syncytial virus (RSV) vaccine, which is a recombinant protein vaccine for adults over 60, in May 2023. No previous reports of polymyalgia rheumatica onset or relapse have been linked to the RSV vaccine. The human proteome shares some peptides with the RSV F antigen, suggesting a high risk of cross-reactivity when using that antigen in vaccination formulations. A 72-year-old man experienced a new onset of bilateral shoulder pain and stiffness three days after receiving the Abrysvo® RSV vaccine. The symptoms lasted more than an hour (up until noon) and interfered with his activities of daily living. Inflammatory markers such as C-reactive protein were elevated. The patient's symptoms and inflammatory marker levels significantly improved with prednisone therapy. In patients with typical PMR symptoms, it is important for clinicians to carefully review immunisation history to rule out any potentially related adverse effects. Vaccines can trigger autoimmune diseases in some individuals.This case report suggests respiratory syncytial virus (RSV) vaccine is among the possible triggers for polymyalgia rheumatica.

Plasmid DNA Encoding the Respiratory Syncytial Virus G Protein Is a Promising Vaccine Candidate