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Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections, particularly affecting young infants, older adults, and individuals with comorbidities. Methods: This document, developed as a consensus by an international group of experts affiliated with the World Association of Infectious Diseases and Immunological Disorders (WAidid), focuses on recent advancements in RSV prevention, highlighting the introduction of monoclonal antibodies (mAbs) and vaccines. Results: Historically, RSV treatment options were limited to supportive care and the monoclonal antibody palivizumab, which required multiple doses. Recent innovations have led to the development of long-acting mAbs, such as nirsevimab, which provide season-long protection with a single dose. Nirsevimab has shown high efficacy in preventing severe RSV-related lower respiratory tract infections (LRTIs) in infants, reducing hospitalizations and ICU admissions. Additionally, new vaccines, such as RSVpreF and RSVpreF3, target older adults and have demonstrated significant efficacy in preventing LRTIs in clinical trials. Maternal vaccination strategies also show promise in providing passive immunity to newborns, protecting them during the most vulnerable early months of life. This document further discusses the global burden of RSV, its economic impact, and the challenges of implementing these preventative strategies in different healthcare settings. Conclusions: The evidence supports the integration of both passive (mAbs) and active (vaccines) immunization approaches as effective tools to mitigate the public health impact of RSV. The combined use of these interventions could substantially reduce RSV-related morbidity and mortality across various age groups and populations, emphasizing the importance of widespread immunization efforts. [ABSTRACT FROM AUTHOR]

Older age and comorbid conditions increase risk for severe for respiratory syncytial virus (RSV). Skilled nursing facilities (SNFs) and assisted living (AL) facilities represent an intersection of risk factors. In a 3-year prospective study in Rochester, New York, we compared the population-based incidence of RSV-associated hospitalization for community-dwelling (CD), SNF, and AL adults aged ≥65 years. Their median ages were 76, 83 and 86 years, respectively, and dementia and congestive heart failure (CHF) were more prevalent among SNF and AL residents. The average annual incidences were 117 (95% confidence interval, 104–132), 440 (307–629) and 740 per 100 000 persons (523–1045), respectively, for CD, SNF, and AL adults aged ≥65 years, demonstrating a need for unequivocal RSV vaccine recommendations in SNF and AL residents. [ABSTRACT FROM AUTHOR]

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.

Introduction: 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. Methods: 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. Results: The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days postimmunization. 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. Conclusion: These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted. [ABSTRACT FROM AUTHOR]

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborns and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine (brand name ABRYSVO) represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines. [ABSTRACT FROM AUTHOR]

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. Methods This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12–18 months after first vaccination. Results The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12–18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. Conclusions This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. Clinical Trials Registration NCT04138056. [ABSTRACT FROM AUTHOR]

Ipsilateral axillary adenopathy post-COVID mRNA vaccine has been widely reported and guidelines for management have been established. Isolated changes of axillary tail trabecular thickening without associated adenopathy in the breast present a diagnostic dilemma and no official guidelines have thus far been reported. This finding has been reported after COVID mRNA vaccine and has never been reported with any other vaccine. We report on a patient with such changes on screening mammography 1.5 months after the fifth dose of a COVID-mRNA vaccine and 1 week after RSV vaccine. This raises the possibility that such changes can be seen with vaccines other than the COVID mRNA series of vaccines. The main differential diagnosis includes mastitis and inflammatory breast cancer. The transient nature of this finding with spontaneous resolution at diagnostic mammography and the vaccination history helps to establish the diagnosis and exclude breast cancer.

RSV infection causes severe respiratory illness and mortality in the elderly, especially in the presence of comorbidities. Early identification of infection would result in appropriate clinical-therapeutic management, avoiding hospitalizations, the risk of healthcare-associated infections, and inappropriate antibiotic prescriptions, thus reducing healthcare costs and fighting antimicrobial resistance. The aim of this study was to assess RSV hospitalizations in subjects >64 years hospitalized in a large tertiary care hospital in Southern Italy, in order to assess their usefulness as a proxy for targeting a potential vaccination strategy. Fifty-two RSV-positive patients were identified from the 2014–2015 to the 2022–2023 seasons. RSV type B was found in 71.2% of cases. The median age was 78 years (IQR: 72–84) and 40.4% of the subjects had at least one comorbidity; 5.8% needed intensive care. The use of combined rapid tests for SARS-CoV-2/influenza/RSV identification in primary care settings may contribute to an improved definition of the burden of RSV in the elderly. The implementation of an anti-RSV vaccination strategy in the elderly population would reduce direct and indirect infection costs. More robust epidemiological data in Italy are needed for targeted preventive strategies.

Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines. [ABSTRACT FROM AUTHOR]

Although respiratory syncytial virus (RSV) vaccine development initiatives have existed for half a century, no candidate has been approved for application at all ages from neonates to children. Developing an effective and safe RSV vaccine for pediatric use is challenging owing to RSV-associated disease and vaccine-enhanced disease (VED). We aimed to design an RSV vaccine, KD-409, by structurally incorporating the F ectodomain and G protein central conserved domain without the CX3C chemokine motif and test its efficacy and safety. KD-409 formed rosette particles or trimmers. KD-409 immunization of mice mainly induced anti-RSV F protein IgG. The induced anti-F antibodies had a higher IgG2a/IgG1 ratio than pre-fusion F, suggesting that they induced Th1-dominant immunity. Active and passive immunities were assessed by analyzing the viral titers in BALB/c mice intranasally challenged with RSV after intramuscular KD-409 immunization and pups derived from mothers who were intramuscularly vaccinated with KD-409 twice, respectively. KD-409 was more effective than post-fusion F and had a lower minimum effective dose than pre-fusion F. Thus, KD-409 demonstrated great potential as a novel RSV vaccine candidate, outperforming existing RSV F-based candidates. Our findings provide a promising strategy to overcome RSV-associated acute lower respiratory infections without the risk of VED associated with traditional approaches. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) remains the primary cause of lower respiratory tract infections, particularly in infants and the elderly. In this study, we employed reverse genetics to generate a chimeric influenza virus expressing neuraminidase‐3F protein conjugate with three repeats of the RSV F protein protective epitope inserted into the NA gene of A/California/7/2009 ca (CA/AA ca), resulting in rFlu/RSV/NA‐3F (hereafter, rFRN3). The expression of NA‐3F protein was confirmed by Western blotting. The morphology and temperature‐sensitive phenotype of rFRN3 were similar to CA/AA ca. Its immunogenicity and protective efficiency were evaluated in BALB/c mice and cotton rats. Intranasal administration of rFRN3 elicited robust humoral, cellular, and to some extent, mucosal immune responses. Compared to controls, rFRN3 protected animals from RSV infection, attenuated lung injury, and reduced viral titers in the nose and lungs post‐RSV challenge. These results demonstrate that rFRN3 can trigger RSV‐specific immune responses and thus exhibits potent protective efficacy. The "dual vaccine" approach of a cold‐adapted influenza vector RSV vaccine will improve the prophylaxis of influenza and RSV infection. rFRN3 thus warrants further clinical investigations as a candidate RSV vaccine. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes infections of the lower respiratory tract. A group particularly vulnerable to severe infection are young children under 2 years of age and the elderly. The infection can cause the entire spectrum of respiratory symptoms from upper respiratory tract infections to severe courses requiring assisted breathing. Until recently, the only form of protection against infection was passive immunization, i.e. administration of immunoglobulins. Chief among these are palivizumab and nirsevimab. In May u June 2023, the Food and Drug Administration (FDA) approved for use 2 vaccines against RSV are Arexvy and Abrysvo. In this study, we focus on presenting and describing the clinical evidence supporting the effectiveness of these immunization methods. [ABSTRACT FROM AUTHOR]

RSV infection causes severe respiratory illness and mortality in the elderly, especially in the presence of comorbidities. Early identification of infection would result in appropriate clinical-therapeutic management, avoiding hospitalizations, the risk of healthcare-associated infections, and inappropriate antibiotic prescriptions, thus reducing healthcare costs and fighting antimicrobial resistance. The aim of this study was to assess RSV hospitalizations in subjects >64 years hospitalized in a large tertiary care hospital in Southern Italy, in order to assess their usefulness as a proxy for targeting a potential vaccination strategy. Fifty-two RSV-positive patients were identified from the 2014–2015 to the 2022–2023 seasons. RSV type B was found in 71.2% of cases. The median age was 78 years (IQR: 72–84) and 40.4% of the subjects had at least one comorbidity; 5.8% needed intensive care. The use of combined rapid tests for SARS-CoV-2/influenza/RSV identification in primary care settings may contribute to an improved definition of the burden of RSV in the elderly. The implementation of an anti-RSV vaccination strategy in the elderly population would reduce direct and indirect infection costs. More robust epidemiological data in Italy are needed for targeted preventive strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections globally, with most RSV-related deaths occurring in infants

The article discusses the burden of respiratory syncytial virus (RSV) infections in older adults globally, highlighting the significant impact on hospitalizations and deaths. It also examines the efficacy and safety of three RSV vaccines approved for older adults, with data from clinical trials and real-world observational studies. The text provides recommendations for RSV vaccination in older adults with specific risk factors and chronic conditions, as well as considerations for travelers, including timing of vaccination and destination-specific risks. The article emphasizes the need for further research on vaccine effectiveness, safety, and optimal dosing regimens to inform broader vaccination strategies. [Extracted from the article]

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections, particularly affecting young infants, older adults, and individuals with comorbidities. Methods: This document, developed as a consensus by an international group of experts affiliated with the World Association of Infectious Diseases and Immunological Disorders (WAidid), focuses on recent advancements in RSV prevention, highlighting the introduction of monoclonal antibodies (mAbs) and vaccines. Results: Historically, RSV treatment options were limited to supportive care and the monoclonal antibody palivizumab, which required multiple doses. Recent innovations have led to the development of long-acting mAbs, such as nirsevimab, which provide season-long protection with a single dose. Nirsevimab has shown high efficacy in preventing severe RSV-related lower respiratory tract infections (LRTIs) in infants, reducing hospitalizations and ICU admissions. Additionally, new vaccines, such as RSVpreF and RSVpreF3, target older adults and have demonstrated significant efficacy in preventing LRTIs in clinical trials. Maternal vaccination strategies also show promise in providing passive immunity to newborns, protecting them during the most vulnerable early months of life. This document further discusses the global burden of RSV, its economic impact, and the challenges of implementing these preventative strategies in different healthcare settings. Conclusions: The evidence supports the integration of both passive (mAbs) and active (vaccines) immunization approaches as effective tools to mitigate the public health impact of RSV. The combined use of these interventions could substantially reduce RSV-related morbidity and mortality across various age groups and populations, emphasizing the importance of widespread immunization efforts.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections globally, with most RSV-related deaths occurring in infants < 6 months of age. The highest burden of RSV is in low-and-middle income countries, and in sub-Saharan Africa, RSV may be responsible for almost half of all hospital admissions with severe or very severe pneumonia among infants under 1 year. There is a maternal RSV vaccine on the horizon. Our study objective was to better understand how lessons learned from the COVID-19 vaccine experience rollout among pregnant and lactating people in Kenya could inform future maternal RSV vaccine rollout. Methods: This qualitative study interviewed 16 healthcare providers including doctors, nurses, midwives, community health workers, and vaccinators. Participants were recruited from two counties in Kenya and included healthcare providers that served diverse communities. A grounded theory approach was used to analyze the data. Results: As healthcare providers interviewed were instrumental in COVID-19 vaccine rollout among pregnant women in Kenya, they provided lessons learned from the COVID-19 vaccine experience to inform future maternal RSV vaccine rollout. Community sensitization emerged as the most critical lesson learned, including communication, mobilization, and education. Using communication to ensure community awareness of RSV, community awareness of RSV harms and benefits of RSV maternal vaccines, and providing up-to-date, clear information about maternal RSV vaccines emerged as lessons. Related to mobilization, participants identified the need for healthcare providers and community leaders to gain the trust of communities, and the importance of routinizing the vaccine. Finally, for education, participants outlined critical questions patients would have about a maternal RSV vaccine, including those related to vaccine safety concerns, duration of protection, and vaccine dosing. Conclusions: This is one of the first studies that has examined how lessons learned from the COVID-19 vaccine rollout for pregnant and lactating women can inform the rollout of future maternal vaccines, including an RSV maternal vaccine. As healthcare providers are directly involved in vaccine rollout, their perspectives are crucial for successful vaccine acceptance. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) constitutes a significant cause of respiratory illness and mortality among older adults, a demographic that is expanding with considerable impact on healthcare systems worldwide. The actual burden of RSV in this population may still be underestimated, owing to factors such as low awareness and suboptimal diagnostic sensitivity in adults, the lack of robust RSV surveillance systems, and the infrequent use of diagnostic testing. Recent advancements in respiratory virus detection have spurred further exploration into appropriate preventive and therapeutic strategies. The recent approval of two vaccines highlights the critical need for the precise estimation of the RSV disease burden to optimize the effectiveness and cost-efficiency of immunization programs. This narrative review aimed to summarize the existing knowledge of the RSV burden in adults with a particular focus on older adults, incorporating data from Korea. Overall, current estimates indicate that the annual RSV attack rate in the general adult population ranges from 1 - 7%, increasing to approximately 4 - 10% among elderly and high-risk groups. The in-hospital mortality rate can be estimated to be around 7 - 10%, rising up to 40% among intensive care unit-admitted patients. To elucidate RSV’s disease burden, further continuing research, including population-based studies, is necessary. [ABSTRACT FROM AUTHOR]

Background In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 μg RSVPreF3-AS01E formulation. Methods In total, 122 older adults (60–80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 μg RSVPreF3 antigen), received an additional 120 μg RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 μg RSVPreF3-AS01E doses until 1 month after dose 3. Results Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1. Conclusions Revaccination with 120 μg RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults. Clinical Trials Registration NCT04657198; EudraCT, 2020-000692-21. [ABSTRACT FROM AUTHOR]

Introduction: 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. Case description: 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. Conclusion: In patients with typical PMR symptoms, it is important for clinicians to carefully review immunisation history to rule out any potentially related adverse effects.

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborns and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine (brand name ABRYSVO) represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines.

Respiratory syncytial virus (RSV) causes infections of the lower respiratory tract. A group particularly vulnerable to severe infection are young children under 2 years of age and the elderly. The infection can cause the entire spectrum of respiratory symptoms from upper respiratory tract infections to severe courses requiring assisted breathing. Until recently, the only form of protection against infection was passive immunization, i.e. administration of immunoglobulins. Chief among these are palivizumab and nirsevimab. In May u June 2023, the Food and Drug Administration (FDA) approved for use 2 vaccines against RSV are Arexvy and Abrysvo. In this study, we focus on presenting and describing the clinical evidence supporting the effectiveness of these immunization methods.

Respiratory syncytial virus (RSV) is widely known as a frequent cause of respiratory distress among adults, particularly in older people. Recent years have witnessed several improvements in respiratory virus detection, leading to more questions about therapeutic management strategies. This narrative review focuses on the RSV burden in older people and adults with risk factors and provides an update on the main recent developments regarding managing this infection. A comprehensive PubMed search was conducted till August 2023 to identify studies on RSV among the adult population. We included observational studies, RCTs on vaccines, and different therapies. This review should give clinicians an overview of RSV epidemiology and burden among older people and adults with pre-existing risk factors, the most recent randomized clinical trials on RSV vaccines, and the existing data on the different therapeutics existing and under development. There is a growing body of evidence on RSV burden in adults. The landscape of preventive and curative treatments is quickly evolving. [ABSTRACT FROM AUTHOR]

Although respiratory syncytial virus (RSV) vaccine development initiatives have existed for half a century, no candidate has been approved for application at all ages from neonates to children. Developing an effective and safe RSV vaccine for pediatric use is challenging owing to RSV-associated disease and vaccine-enhanced disease (VED). We aimed to design an RSV vaccine, KD-409, by structurally incorporating the F ectodomain and G protein central conserved domain without the CX3C chemokine motif and test its efficacy and safety. KD-409 formed rosette particles or trimmers. KD-409 immunization of mice mainly induced anti-RSV F protein IgG. The induced anti-F antibodies had a higher IgG2a/IgG1 ratio than pre-fusion F, suggesting that they induced Th1-dominant immunity. Active and passive immunities were assessed by analyzing the viral titers in BALB/c mice intranasally challenged with RSV after intramuscular KD-409 immunization and pups derived from mothers who were intramuscularly vaccinated with KD-409 twice, respectively. KD-409 was more effective than post-fusion F and had a lower minimum effective dose than pre-fusion F. Thus, KD-409 demonstrated great potential as a novel RSV vaccine candidate, outperforming existing RSV F-based candidates. Our findings provide a promising strategy to overcome RSV-associated acute lower respiratory infections without the risk of VED associated with traditional approaches.

Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines.

Respiratory syncytial virus is the major cause of respiratory viral infections, particularly in infants, immunocompromised populations, and the elderly (over 65 years old), the prevention of RSV infection has become a priority. In this study, we generated a chimeric influenza virus, termed LAIV/RSV/HA-3F, using reverse genetics technology which contained three repeats of the RSV fusion protein neutralizing epitope site II to the N terminal in the background of the hemagglutinin (HA) gene of cold adapted influenza vaccine A/California/7/2009 ca. LAIV/RSV/HA-3F exhibited cold-adapted (ca) and attenuated (att) phenotype. BALB/c mice immunized intranasally with LAIV/RSV/HA-3F showed robust immunogenicity, inducing viral-specific antibody responses against both influenza and RSV, eliciting RSV-specific humoral, cellular and mucosal immune responses. LAIV/RSV/HA-3F also conferred protection as indicated by reduced viral titers and improved lung histopathological alterations against live RSV virus challenge. Mechanismly, single-cell RNA sequencing (scRNA-seq) and single-cell T cell antigen receptor (TCR) sequencing were employed to characterize the immune responses triggered by chimeric RSV vaccine, displaying that LAIV/RSV/HA-3F provided protection mainly via interferon-γ (IFN-γ). Moreover, we found that LAIV/RSV/HA-3F significantly inhibited viral replication in the challenged lung and protected against subsequent RSV challenge in cotton rats without causing lung disease. Taken together, our findings demonstrated that LAIV/RSV/HA-3F has potential as a promising bivalent vaccine with dual purpose candidate for the prevention of influenza and RSV, and preclinical and clinical studies warrant further investigations. • We generated a chimeric influenza virus LAIV/RSV/HA-3F carrying three repeats of RSV F neutralizing epitope site II. • LAIV/RSV/HA-3F elicited vigorous humoral, cellular and mucosal immune responses. • LAIV/RSV/HA-3F protected BALB/c mice and cotton rats from RSV infection without causing ERD. • LAIV/RSV/HA-3F provided protection mainly depended on IFN-γ signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.Methods: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.Results: Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.Conclusions: RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.Clinical Trials Registration: NCT04071158. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.Methods: In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo.Results: Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%-53.2%) versus placebo (0%-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one.Conclusions: The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women.Clinical Trials Registration: NCT03674177. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) typically results in mild cold-like symptoms; however, it can lead to severe complications and hospitalization in patients who are 60 years of age and older with long-term health conditions., Objective: The aim of this study was to assess patient knowledge about RSV and to provide patients with information about the virus and the vaccination., Methods: A multisite cross-sectional pilot study was conducted from September 12, 2023, to March 11, 2024, in the independent community pharmacy setting. Included were all patients aged 60 years and older who consented to filling out the 14-question survey. Excluded were patients who declined to take the survey. Patients completed the survey either on paper or electronically, and the survey included initial consent, demographic information, past medical history, knowledge of RSV, consent to vaccine administration, and reasons for refusal, if applicable. At the end of the survey, patients could consent to vaccine administration onsite and were provided with an educational handout., Results: The primary outcome revealed that 78% of participants had not received any education from their healthcare provider about RSV. Additionally, 70% correctly identified ways RSV might spread, 60% reported knowing how to protect themselves, and 58% correctly indicated that a previous RSV infection does not provide immunity. As for the secondary outcomes, 63% of participants consented to receive the vaccine on the day of the survey., Conclusion: The study underscores the critical role of community pharmacies in healthcare delivery and the need for enhanced educational efforts to support vaccination programs., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The FDA's approval of Pfizer's new respiratory syncytial virus (RSV) prefusion (preF) vaccine, Abrysvo, marks a critical milestone in infant health and well-being by preventing lower respiratory tract infections in the most vulnerable. The vaccine has been approved for administration to pregnant women at 32 to 36 weeks of gestation and elderly people over 60. This review explores the Abrysvo vaccine, detailing its mechanism, efficacy, safety, and adverse events. It aims to inform healthcare providers about this vital method for safeguarding infant respiratory health through maternal immunization., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

Since the development of the first vaccine against smallpox over two centuries ago, vaccination strategies have been at the forefront of significantly impacting the incidences of infectious diseases globally. However, the increase in the human population, deforestation and climate change, and the rise in worldwide travel have favored the emergence of new viruses with the potential to cause pandemics. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is a cruel reminder of the impact of novel pathogens and the suboptimal capabilities of conventional vaccines. Therefore, there is an urgent need to develop new vaccine strategies that allow the production of billions of doses in a short duration and are broadly protective against emerging and re‐emerging infectious diseases. Extensive knowledge of the molecular biology and immunology of adenoviruses (Ad) has favored Ad vectors as platforms for vaccine design. The Ad‐based vaccine platform represents an attractive strategy as it induces robust humoral and cell‐mediated immune responses and can meet the global demand in a pandemic situation. This review describes the status of Ad vector‐based vaccines in preclinical and clinical studies for current and emerging respiratory viruses, particularly coronaviruses, influenza viruses and respiratory syncytial viruses. [ABSTRACT FROM AUTHOR]

• Intranasal Mnull RSV vaccine moderately improved most endpoints after RSV infection. • Intrapulmonary Mnull RSV vaccination induced RSV NA responses lasting >4–6 months. • Intrapulmonary Mnull RSV vaccination markedly reduced tachypnea after RSV infection. • Intrapulmonary Mnull RSV vaccination prevented viral replication after RSV infection. • Intrapulmonary Mnull RSV vaccination reduced work of breathing after RSV infection. Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted ("Mnull RSV"). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4–6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans. [ABSTRACT FROM AUTHOR]

• A preventive RSV vaccine for use in infants is an important unmet medical need. • Past studies observed vaccine-associated ERD after RSV infection in RSV-naïve infants. • Risk of vaccine-associated ERD has stalled efforts to develop new candidate vaccines. • Understanding the immunopathology of ERD has guided renewed efforts at vaccine development. • This report summarizes presentations and discussion of a recent VRBPAC meeting. Respiratory syncytial virus (RSV), is a common cause of serious acute lower respiratory tract illness in infants and young children, causing substantial morbidity and mortality globally. Treatment is mainly supportive and currently there is no licensed preventive vaccine. Clinical trials conducted in the 1960s evaluating a formalin-inactivated RSV vaccine (FI-RSV) in RSV-naïve infants resulted in observations of enhanced respiratory disease (ERD) following subsequent natural RSV infection in vaccinees. In these studies, infants immunized with FI-RSV had higher rates of severe RSV disease compared with controls. This outcome redirected focus on identifying the immunologic mechanisms that precipitated ERD as a prerequisite to further vaccine development. Improved understanding of the immunopathogenesis of ERD derived from animal models has stimulated development of new candidate vaccines and engendered discussions among RSV experts about the safety data needed to advance these products into the clinic, and ultimately, into the target population of RSV-naïve infants. The recognition that multiple products would soon be ready for testing in infants and children prompted the FDA to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting to seek perspectives and advice of experts regarding the types and extent of preclinical and clinical data that might be needed to support testing in RSV-naïve infants for specific types of candidate RSV vaccines. Committee members agreed that, if certain conditions are met in preclinical and early clinical studies, it would be reasonable to move forward from studies in adults and older children and into clinical trials evaluating vaccine safety and efficacy in RSV-naïve infants. Herein, we review and summarize perspectives on the discussion regarding recommendations for RSV vaccine development in this population. [ABSTRACT FROM AUTHOR]

Objective: In a population-based cohort study, we determined the association between the age at first severe respiratory syncytial virus (RSV) disease and subsequent asthma.Methods: Incidence rates and rate ratios of the first asthma-associated hospitalization after 2 years of age in children hospitalized for RSV disease at <3 months, 3 to <6 months, 6 to <12 months, and 12-24 months of age were calculated.Results: The incidence of asthma-associated hospitalization per 1000 child-years among children hospitalized for RSV disease at <3 months of age was 0.5 (95% confidence interval [CI], .2-.7); at 3 to <6 months of age, 0.9 (95% CI,.5-1.3); at 6 to <12 months of age, 2.0 (95% CI, 1.4-2.7); and at 12-24 months of age, 1.7 (95% CI, 1.0-2.5). The rate ratio of hospitalization for asthma was 2-7-fold greater among children hospitalized for RSV disease at ages ≥6 months than that among those hospitalized for RSV disease at ages 0 to <6 months.Conclusions: Although the burden of RSV disease is highest in children aged <6 months, the burden of subsequent asthma is higher in children who develop RSV disease at ages ≥6 months. [ABSTRACT FROM AUTHOR]

Most individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV naïve animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation stabilized pre-fusion F protein stimulated high titers of neutralizing antibodies (NA) while an immunization with post-F containing VLPs or a second RSV infection only weakly stimulated NA even though total anti-F protein IgG antibody levels in both VLP immunized animals were similar. Furthermore, single Pre-F or Post-F VLP immunization of RSV previously infected (primed) animals resulted in total anti-F antibody titers that were 10 to 12-fold higher than titers after a VLP prime and boost of RSV naïve animals or after two consecutive RSV infections. The avidities of serum antibodies as well as numbers of splenic B cells and bone marrow cells after different immunization protocols were also assessed. The combined results show that RSV infection can quite effectively prime animals for the production of protective antibodies that can be efficiently activated by a Pre-F VLP boost but not by a Post-F VLP boost or a second RSV infection. [ABSTRACT FROM AUTHOR]

The induction of a dominant Th2-type response is the main cause of harmful inflammation in respiratory syncytial virus (RSV) vaccine trials. A balanced Th1 versus Th2 immune response is needed for a safe and effective RSV vaccine. In this study, we evaluated the potential of a recombinant protein SBP-FG as a vaccine candidate with the main focus on shifting the harmful Th2 response to a Th1 response. SBP-FG consists of epitopes from RSV fusion (F) and attachment (G) proteins conjugated to the N-terminus of HBsAg-binding protein (SBP). SBP-FG induced significantly stronger immune responses assessed at the level of total IgG, IgA and neutralizing antibodies as compared with formalin-inactivated RSV (FI-RSV) and live RSV. Analysis of IgG isotypes, lung cytokines and T helper cells showed that SBP-FG induced a dominant Th1-type response. Further, SBP-FG immunized mice showed significantly reduced lung eosinophilia, reduced viral multiplication in lungs after challenge infection and provided protection against RSV infection. These results suggest that SBP-FG can be developed into a safe and effective vaccine against RSV. However, more studies are required to further evaluate SBP-FG as a potent vaccine candidate against RSV. [ABSTRACT FROM AUTHOR]

Objective Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules. Methods Placebo, or vaccine with 60 μg or 120 μg RSV F protein and 0.2, 0.4, or 0.8 mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18–35 years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91. Results All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120 μg RSV F protein and 0.4 mg aluminum, but persistence through 91 days was modestly (∼25%) superior following two doses of 60 μg RSV F protein and 0.8 mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p = 0.009 overall) over the Day 0 through 90 period. Conclusions RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120 μg RSV F and 0.4 mg aluminum, which achieved peak immune responses in 14 days and sufficient persistence through 91 days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686 . [ABSTRACT FROM AUTHOR]