Respiratory Syncytial Virus Vaccine Research Articles

Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F2-F1 linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F structures and one hMPV-F structure), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identify three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induce robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development.

A self-amplifying RNA RSV prefusion-F vaccine elicits potent immunity in pre-exposed and naïve non-human primates.

Newly approved subunit and mRNA vaccines for respiratory syncytial virus (RSV) demonstrate effectiveness in preventing severe disease, with protection exceeding 80% primarily through the generation of antibodies. An alternative vaccine platform called self-amplifying RNA (saRNA) holds promise in eliciting humoral and cellular immune responses. We evaluate the immunogenicity of a lipid nanoparticle (LNP)-formulated saRNA vaccine called SMARRT.RSV.preF, encoding a stabilized form of the RSV fusion protein, in female mice and in non-human primates (NHPs) that are either RSV-naïve or previously infected. Intramuscular vaccination with SMARRT.RSV.preF vaccine induces RSV neutralizing antibodies and cellular responses in naïve mice and NHPs. Importantly, a single dose of the vaccine in RSV pre-exposed NHPs elicits a dose-dependent anamnestic humoral immune response comparable to a subunit RSV preF vaccine. Notably, SMARRT.RSV.preF immunization significantly increases polyfunctional RSV.F specific memory CD4+ and CD8+ T-cells compared to RSV.preF protein vaccine. Twenty-four hours post immunization with SMARRT.RSV.preF, there is a dose-dependent increase in the systemic levels of inflammatory and chemotactic cytokines associated with the type I interferon response in NHPs, which is not observed with the protein vaccine. We identify a cluster of analytes including IL-15, TNFα, CCL4, and CXCL10, whose levels are significantly correlated with each other after SMARRT.RSV.preF immunization. These findings suggest saRNA vaccines have the potential to be developed as a prophylactic RSV vaccine based on innate, cellular, and humoral immune profiles they elicit.

Burden of Respiratory Syncytial Virus-Associated Hospitalizations in US Adults, October 2016 to September 2023.

Respiratory syncytial virus (RSV) infection can cause severe illness in adults. However, there is considerable uncertainty in the burden of RSV-associated hospitalizations among adults prior to RSV vaccine introduction. To describe the demographic characteristics of adults hospitalized with laboratory-confirmed RSV and to estimate annual rates and numbers of RSV-associated hospitalizations, intensive care unit (ICU) admissions, and in-hospital deaths. This cross-sectional study used data from the RSV Hospitalization Surveillance Network (RSV-NET), a population-based surveillance platform that captures RSV-associated hospitalizations in 58 counties in 12 states, covering approximately 8% of the US population. The study period spanned 7 surveillance seasons from 2016-2017 through 2022-2023. Included cases from RSV-NET were nonpregnant hospitalized adults aged 18 years or older residing in the surveillance catchment area and with a positive RSV test result. Laboratory-confirmed RSV-associated hospitalization, defined as a positive RSV test result within 14 days before or during hospitalization. Hospitalization rates per 100 000 adult population, stratified by age group. After adjusting for test sensitivity and undertesting for RSV in adults hospitalized with acute respiratory illnesses, rates were extrapolated to the US population to estimate annual numbers of RSV-associated hospitalizations. Clinical outcome data were used to estimate RSV-associated ICU admissions and in-hospital deaths. From the 2016 to 2017 through the 2022 to 2023 RSV seasons, there were 16 575 RSV-associated hospitalizations in adults (median [IQR] age, 70 [58-81] years; 9641 females [58.2%]). Excluding the 2020 to 2021 and the 2021 to 2022 seasons, when the COVID-19 pandemic affected RSV circulation, hospitalization rates ranged from 48.9 (95% CI, 33.4-91.5) per 100 000 adults in 2016 to 2017 to 76.2 (95% CI, 55.2-122.7) per 100 000 adults in 2017 to 2018. Rates were lowest among adults aged 18 to 49 years (8.6 [95% CI, 5.7-16.8] per 100 000 adults in 2016-2017 to 13.1 [95% CI, 11.0-16.1] per 100 000 adults in 2022-2023) and highest among adults 75 years or older (244.7 [95% CI, 207.9-297.3] per 100 000 adults in 2022-2023 to 411.4 [95% CI, 292.1-695.4] per 100 000 adults in 2017-2018). Annual hospitalization estimates ranged from 123 000 (95% CI, 84 000-230 000) in 2016 to 2017 to 193 000 (95% CI, 140 000-311 000) in 2017 to 2018. Annual ICU admission estimates ranged from 24 400 (95% CI, 16 700-44 800) to 34 900 (95% CI, 25 500-55 600) for the same seasons. Estimated annual in-hospital deaths ranged from 4680 (95% CI, 3570-6820) in 2018 to 2019 to 8620 (95% CI, 6220-14 090) in 2017 to 2018. Adults 75 years or older accounted for 45.6% (range, 43.1%-48.8%) of all RSV-associated hospitalizations, 38.6% (range, 36.7%-41.0%) of all ICU admissions, and 58.7% (range, 51.9%-67.1%) of all in-hospital deaths. In this cross-sectional study of adults hospitalized with RSV before the 2023 introduction of RSV vaccines, RSV was associated with substantial burden of hospitalizations, ICU admissions, and in-hospital deaths in adults, with the highest rates occurring in adults 75 years or older. Increasing RSV vaccination of older adults has the potential to reduce associated hospitalizations and severe clinical outcomes.

Immune Responses to Respiratory Syncytial Virus Vaccines: Advances and Challenges

Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory infections, particularly in children and the elderly. This virus primarily infects ciliated epithelial cells and activates alveolar macrophages and dendritic cells, triggering an innate antiviral response that releases pro-inflammatory cytokines. However, immunity generated by infection is limited, often leading to reinfection throughout life. This review focuses on the immune response elicited by newly developed and approved vaccines against RSV. A comprehensive search of clinical studies on RSV vaccine candidates conducted between 2013 and 2024 was performed. There are three primary target groups for RSV vaccines: pediatric populations, infants through maternal immunization, and the elderly. Different vaccine approaches address these groups, including subunit, live attenuated or chimeric, vector-based, and mRNA vaccines. To date, subunit RSV vaccines and the mRNA vaccine have been approved using the pre-fusion conformation of the F protein, which has been shown to induce strong immune responses. Nevertheless, several other vaccine candidates face challenges, such as modest increases in antibody production, highlighting the need for further research. Despite the success of the approved vaccines for adults older than 60 years and pregnant women, there remains a critical need for vaccines that can protect children older than six months, who are still highly vulnerable to RSV infections.

Infectivity and immunogenicity of live-attenuated respiratory syncytial virus vaccines in HIV-exposed uninfected children

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. HIV-exposed uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines. Methods In a pooled analysis of clinical trials of seven live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein IgG antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season. Results Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs. 88%) and anti-RSV F IgG (70% vs. 89%) titers at 56 days after vaccination. Conclusions Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early-childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.

Landscape of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirusgenus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.

Novel intercellular spread mode of respiratory syncytial virus contributes to neutralization escape

Developing widely used respiratory syncytial virus (RSV) vaccines remains a significant challenge, despite the recent authorization of two pre-F vaccines for elderly adults. Previous reports have suggested that even when vaccine-induced immunity generates high titers of potent neutralizing antibodies targeting the pre-F protein, it may not fully inhibit breakthrough of RSV infections. This incomplete inhibition of RSV breakthrough infections can lead to an increased risk of enhanced respiratory disease (ERD) in vaccinated individuals. The reasons why potent neutralizing antibodies cannot fully prevent RSV breakthrough infections are not yet clear. In an attempt to explain this phenomenon, we investigated the effect of potent neutralizing antibodies on the intercellular spread of RSV. Our findings indicated that a specific titer of potent neutralizing antibodies, such as 5C4, could block certain modes of intercellular spread, such as the diffusion of cell-free virions and the delivery of virions through filopodia. However, these antibodies did not fully inhibit the entire process of intercellular spread. Through the use of super-resolution imaging techniques, we observed a novel and efficient spread mode called the transition of viral materials through intercellular nanotubes (TVMIN), independent of virions and insensitive to the presence of antibodies. TVMIN allowed RSV-infected cells to directly transfer viral materials to neighboring cells via intercellular nanotubes that are rich in microfilaments. TVMIN began as early as 5 h post-infection (h.p.i.) and rapidly initiated infection in recipient cells. Our data provided new insights into the intercellular spread of RSV and might help explain the occurrence of breakthrough infections.

Determinants of maternal acceptance of respiratory syncytial virus vaccination: knowledge gaps and influence of healthcare professionals

Determinants of maternal acceptance of respiratory syncytial virus vaccination: knowledge gaps and influence of healthcare professionals

Prospective Attitudes Towards Respiratory Syncytial Virus (RSV) Vaccine in Pregnant Women in Greece

Respiratory Syncytial Virus (RSV) is a common respiratory pathogen with high morbidity and mortality, especially in children under two years of age. Severe RSV infection poses a significant threat to healthcare systems, making vaccination an utmost need. In August 2023, the U.S. FDA approved an RSV maternal vaccine to prevent lower respiratory tract disease (LRTD) in infants throughout their first six months of life. This cross-sectional survey was designed to evaluate pregnant women’s willingness to receive the vaccine during pregnancy. An anonymous survey was administered from April 2023 to December 2023 to pregnant women aged above 16 years old attending gynecology wards of randomly selected public and private hospitals in Crete. The primary outcome was the intention to receive the vaccine. Univariable and multivariable analyses were carried out to identify factors associated with the intention to get vaccinated. Questionnaires were distributed to a sample of 335 pregnant females who agreed to participate in this study. The intention to get vaccinated against RSV was positively associated with educational level, the presence of school-age children, RSV infection awareness, intention to get routine pregnancy vaccines according to the National Immunization Program (NIP), and previous vaccination against COVID-19. The majority of pregnant females were not familiar with the term RSV and the upcoming vaccine. An educational campaign regarding RSV infection and its vaccine is required to improve women’s perceptions and to support healthcare workers in promoting it upon its availability in Greece.

The Development of Animal Models for Respiratory Syncytial Virus (RSV) Infection and Enhanced RSV Disease

The development of immunoprophylactic products against respiratory syncytial virus (RSV) has resulted in notable advancements, leading to an increased demand for preclinical experiments and placing greater demands on animal models. Nevertheless, the field of RSV research continues to face the challenge of a lack of ideal animal models. Despite the demonstration of efficacy in animal studies, numerous RSV vaccine candidates have been unsuccessful in clinical trials, primarily due to the lack of suitable animal models. The most commonly utilized animal models for RSV research are cotton rats, mice, lambs, and non-human primates. These animals have been extensively employed in mechanistic studies and in the development and evaluation of vaccines and therapeutics. However, each model only exemplifies some, but not all, aspects of human RSV disease. The aim of this study was to provide a comprehensive summary of the disease symptoms, viral replication, pathological damage, and enhanced RSV disease (ERD) conditions across different RSV animal models. Furthermore, the advantages and disadvantages of each model are discussed, with the intention of providing a valuable reference for related RSV research.

Cost-Effectiveness of Bivalent Respiratory Syncytial Virus Prefusion F Vaccine for Prevention of Respiratory Syncytial Virus Among Older Adults in Greece

Background/Objectives: To evaluate the health benefits, costs, and cost-effectiveness of vaccination with bivalent respiratory syncytial virus stabilized prefusion F vaccine (RSVpreF) for the prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) in Greek adults 60 years of age and older. Methods: A Markov model was adapted to simulate lifetime risk of health and economic outcomes from the public payer’s perspective over a lifetime horizon. Epidemiology, vaccine effectiveness, utilities, and direct medical costs (EUR, 2024) were obtained from published studies, official sources, and local experts. Model outcomes included the number of medically attended RSV cases, stratified by care setting (i.e., hospital, emergency department [ED], outpatient visits [OV]), and attributable RSV-related deaths, costs, life years (LY), quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICERs) of RSVpreF vaccination compared with no vaccination. Results: The model projected 258,170 hospitalizations, 112,248 ED encounters, 1,201,604 OV, and 25,463 deaths related to RSV in Greek older adults resulting in direct medical costs of EUR 1.6 billion over the lifetime horizon. Assuming RSV vaccination would reach the same coverage rates as pneumococcal and influenza programmes, 18,118 hospitalizations, 7874 ED encounters, 48,079 OV, and 1706 deaths could be prevented over the modelled time horizon. The health benefits associated with RSVpreF contributed to an incremental gain of 10,976 LYs and 7230 QALYs compared with no vaccination. The incremental analysis reported that vaccination with RSVpreF was estimated to be a cost-effective strategy resulting in ICERs of EUR 12,991 per LY gained, EUR 19,723 per QALY gained, and EUR 7870 per hospitalized RSV case avoided compared with no vaccination. Conclusions: Vaccination with RSVpreF was a cost-effective strategy for the prevention of RSV disease in Greek adults over 60 years of age. The introduction of RSV vaccination can improve public health by averting RSV cases and deaths and has the potential to fulfil an unmet medical need.

The efficacy of vaccination against respiratory syncytial virus across priority population subgroups

Abstract Background Respiratory syncytial virus (RSV) has recently become a vaccine-preventable disease as two vaccines have been approved for use and a third one is likely to become available by the end of the year. National Immunization Technical Advisory Groups as well as scientific societies across the world have issued recommendations on RSV vaccination that differ in respect to the identification of the target group. The latter has been identified in respect to age or underlying medical conditions mostly according to epidemiological data. In order to strengthen the evidence basis for future decisions, we performed a stratified meta-analysis of efficacy data considering all the three RSV vaccines currently or soon available. Methods We searched Randomized Controlled Trials (RCTs) assessing the efficacy of RSV vaccines in terms of reduction of RSV-related Lower Respiratory Tract Infection (LRTI). The research was conducted on PubMed and clinicaltrial.gov. The extraction of relevant data was stratified by pre-defined age groups (60-69, 70-79, 80+) and presence of underlying conditions increasing the risk for RSV. Results Three RCTs, one for each of the three vaccines, were considered for the quantitative analysis. Considering the overall 60+ population, the efficacy of RSV vaccines was 78% (95%CI 76-86%) in preventing LRTI. Considering the different age groups (60-69, 70-79, 80+), efficacy was respectively 72% (95%CI 53-84%), 90% (95%CI 66-97%) and 57% (95%CI 0-93%). The efficacy in healthy people and those with at least one underlying condition was similar, namely 77% (95%CI 60-87%) and 78% (95%CI 50-90%). Conclusions The available evidence shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. Further studies may contribute to better understanding if the efficacy may change according to individual characteristics, that could be highly relevant in the decision-making process. Key messages • The available evidence from RCTs shows the efficacy of RSV vaccines in reducing LRTI with no differences across different priority groups. • National recommendations on RSV vaccination can be further informed for future studies investigating RSV vaccines efficacy across different subgroups.

New advances in RSV: Is prevention attainable?

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI), hospitalization, and mortality in infants and young children globally. The greatest burden of severe disease and mortality occurs in low-middle income countries (LMICs), with large and vulnerable childhood populations. The highest rates of RSV-hospitalization occur in healthy-term infants under 3 months of age. Preterm infants, children with chronic lung disease of prematurity, Down's syndrome, congenital heart disease, or immunodeficiency also have a higher risk of severe RSV-LRTI. Early-life RSV-LRTI has also been associated with chronic sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment. A RSV pre-fusion (F) maternal vaccine and long-acting monoclonal antibody (nirsevimab) have been licensed for the prevention of RSV-LRTI in infants and young children. Studies show high efficacy and effectiveness particularly for preventing severe RSV-LRTI. Maternal RSV vaccine given at 24-36 weeks of pregnancy was effective in preventing RSV medically attended LRTI and severe RSV-LRTI through 6 months after birth in a phase 3 study conducted in 18 countries over two RSV seasons. Vaccination was safe with no significant difference in adverse events between infants born to mothers who received RSV preF vaccine compared to placebo. A numerical imbalance in preterm births that occurred predominantly in South Africa, unrelated to vaccine timing or gestational age at vaccination and unassociated with mortality, coincided with COVID-19 delta and omicron waves. Nirsevimab, given as a single dose prior or during the RSV season, had high efficacy in preventing RSV-LRTI hospitalization in infants in preterm and in full-term infants, as well as in young children with underlying conditions through 150 days post administration in phase 2 and 3 trials. High effectiveness against hospitalization or severe disease in infants and in at-risk children up to 2 years of age has also been reported in several countries where implementation has occurred. RSV-LRTI is now a preventable disease in infants and young children. Rapid implementation of these highly effective interventions has occurred in many high-income countries, but access remains very limited in LMICs. Access to such RSV preventive interventions is urgently needed for all children to strengthen child health and promote global equity.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

The impact of viral respiratory infection on surgical outcome of cavopulmonary shunt.

Undetected respiratory infections may adversely affect the intrapulmonary resistance after Stage 2 or Stage 3 Fontan palliation. A few studies describe a higher risk for viral pneumonia during respiratory virus season, but none of them have focused on the effect of symptomatic viral pneumonia on in-hospital clinical course after bidirectional Glenn shunt. We analysed 77 patients who underwent bidirectional Glenn shunt surgery. Six patients were detected with pneumonia and proof of viral ribonucleic acid in tracheal mucus in the very early postoperative time. We compared them retrospectively to the remaining 71 patients regarding preoperative inflammatory signs, mortality, paediatric ICU length of stay, and ventilation time. The infection rate was not seasonal dependent. Ventilation time was significantly elongated in the pneumonia group (558 h ± 634 vs. 8.7 h ± 1.9; p < 0.0001) and so was the paediatric ICU length of stay (29 days ± 26 vs. 3 days±1; p = 0.007). Significantly more patients in the pneumonia group required extracorporeal cardiac life support postoperatively. The mortality was significantly increased in patients with pneumonia. Even subclinical viral pneumonia may cause ventilation-to-perfusion mismatch by raising intrapulmonary resistance. Recorded parameters of postoperative paediatric ICU therapy showed a significant impact of a viral pneumonia on patients after bidirectional Glenn shunt. The respiratory syncytial virus vaccination does not protect these patients from infection with other respiratory viruses. The focus should be put on preoperative diagnosis of pulmonary infections in the vulnerable group of patients with univentricular hearts.

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 vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention.

The Cumulative Variations of Respiratory Syncytial Virus Fusion Protein (F) in Ten Consecutive Years in China.

Variations in the fusion (F) protein of respiratory syncytial virus (RSV) with main antigenic sites I-V and Ø may affect the development of RSV vaccines and therapies. In the study, 30 respiratory specimens positive for RSV were randomly selected from children with acute lower respiratory infections (ALRI) in Beijing every year from 2012 to 2021 for F gene sequencing. Then, 300 F gene sequences and 508 uploaded to GenBank from China were subjected to phylogenetic analysis. The results indicated the nucleotide identities were 95.4-100% among 446 sequences of RSV A, and 96.3-100% among 362 of RSV B. The most common variant loci were N80K (100.00%) and R213S (97.76%) for site Ø, and V384I/T (98.43%) for site I among sequences of RSV A, and M152I (100.00%), I185V (100.00%), and L172Q/H (94.48%) for site V, and R202Q (99.45%) for site Ø among sequences of RSV B. N276S appears in 95.29% sequences of RSV A, while S276N and N262 I/S appear in 1.38% and 0.55% sequences of RSV B, respectively. No variation was found in all sequences at the binding sites of 14N4 and motavizumab. There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites.

Limited RSV Vaccine Administration: A Case for Redesigning the Preventive Care Model

In this commentary, the authors describe existing barriers to vaccination access linked to the restriction of pharmacists’ prescribing authority, rationalize the need for more innovative care models to enhance the role of the pharmacist, and outline the framework required for health care redesign to enable nonphysicians to close gaps in preventive care. Regulatory and legal issues challenge care redesign at scale. To illustrate this scalability issue and its downstream impact on public health, real-world data from a large national pharmacy chain in the United States, CVS Pharmacy, were leveraged to examine the influence of state-by-state immunization policies on respiratory syncytial virus vaccination administration during the national rollout for adults. As a result of these policies, preventive care (e.g., vaccination administration) was limited in a vulnerable population.

Induction of neutralizing antibody responses by AAV5-based vaccine for respiratory syncytial virus in mice.

Respiratory Syncytial Virus (RSV) is a significant cause of respiratory illnesses worldwide, particularly in infants and elderly individuals. Despite the burden RSV imposes, effective preventive measures are limited. The research application of adeno-associated virus (AAV) in vaccine platforms has been expanding, and its potential in prevention and treatment has garnered much attention. In this study, we explored the potential application of a recombinant adeno-associated virus 5 (rAAV5) vector-based RSV vaccine, focusing on the expression of the pre-fusion (Pre-F) protein structure. Through intramuscular immunization in mice. The immunogenicity of the vaccine was evaluated in Balb/c mice immunized intramuscularly and intranasal, respectively. The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days post-immunization. Notably, intranasal administration also elicited protective antibodies. Characterization studies confirmed the ability of the vac-cine to express the Pre-F protein and its superior immunogenicity compared to that of full-length F protein. These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted.

A new RSV vaccine (mResvia) for adults ≥60 years old.

The FDA has licensed mResvia (Moderna), an mRNA respiratory syncytial virus (RSV) vaccine, for prevention of lower respiratory tract disease (LRTD) caused by RSV in adults ≥60 years old. It is the first mRNA vaccine to be licensed in the US for this indication. Two recombinant RSV vaccines, Arexvy and Abrysvo, are also available for prevention of RSV LRTD.1 Arexvy is approved for use in adults ≥50 years old.2 Abrysvo is approved for use in adults ≥60 years old and in pregnant women to prevent RSV LRTD in their infants.