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Introduction: Respiratory syncytial virus (RSV) is a common, highly contagious pathogen and a leading cause of serious illness among infants and older adults. While existing scientific evidence has predominantly focused on the epidemiology and disease burden of RSV in infants, data in older adults remain limited in some countries, including those in Southeast Asia (SEA) and the Middle East and North Africa (MENA) region. Here, we outline the key challenges for understanding the burden of RSV in older adults in SEA and the MENA region and we propose opportunities for improving understanding and eventually reducing the impact of RSV. Main Findings and Conclusions: A key challenge identified by the expert group, particularly in older adults, is a lack of awareness (among healthcare professionals, policy makers, and the public) of RSV burden and the associated risks for severe outcomes. This is often confounded by the complexities of underdiagnosis, surveillance limitations, and comorbidities. To address these issues, we suggest medical education initiatives for physicians in SEA and the MENA region to better understand the need to protect older adults from RSV, and encourage more widespread routine testing to better understand the burden of RSV. We also recommend surveillance studies in these regions to provide comprehensive and accurate epidemiological data on RSV in older adults. Finally, in the absence of current surveillance data in these regions, we propose extrapolating existing global data and local pediatric data to inform the likely burden of RSV in older adults. A graphical abstract is available with this article. [ABSTRACT FROM AUTHOR]

The UK is launching a new free vaccination programme against respiratory syncytial virus (RSV) in adults aged 75 or over. This follows the development of safe and effective vaccines against RSV and the growing realisation of the burden of RSV-related disease in older adults—estimated at circa 8000 deaths and 175 000 GP episodes every year in the UK. It is likely that the full burden of RSV-related illness is under-appreciated and under-reported due to a lack of testing and awareness of its dangers in older adults. Healthcare professionals working with older people should be aware of the evidence base and be in a position to advise patients on the risks and benefits of vaccination and nonvaccination. We briefly review the evidence for the safety and effectiveness of the two licensed vaccines against RSV with a special focus on what geriatricians and others working with frailer, older people need to know. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is garnering increasing attention, with a growing number of subunit RSV vaccines under active clinical investigation. However, comprehensive evidence is limited. Methods: We conducted a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov from database inception to 12 January 2024, focusing on published randomized controlled trials (RCTs). Results: A total of 17 studies were included, encompassing assessments of efficacy (5 studies), safety (17 studies), and immunogenicity (12 studies) of RSV subunit vaccines. The pooled risk ratio (RR) for RSV-associated acute respiratory infection (RSV-ARI) with subunit vaccines was 0.31 (95% CI: 0.23–0.43), for RSV-associated lower respiratory tract infection (RSV-LRTI), it was 0.32 (95% CI: 0.22–0.44), and for severe RSV-LRTI (RSV-SLRTI), it was 0.13 (95% CI: 0.06–0.29). There was no significant difference in serious adverse events (SAEs) between the vaccine and placebo groups, with a pooled RR of 1.05 (95% CI: 0.98–1.14). The pooled standardized mean difference (SMD) for the geometric mean titer (GMT) of neutralizing antibodies was 2.89 (95% CI: 2.43−3.35). Conclusion: Subunit RSV vaccines exhibit strong efficacy, favorable safety profiles, and robust immunogenicity. Future research should focus on the cost-effectiveness of various vaccines to enhance regional and national immunization strategies. [ABSTRACT FROM AUTHOR]

IntroductionRespiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.MethodsHere, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.ResultsThe results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.DiscussionThe results from this study support further NP-S177Q vaccine candidate development.

BackgroundThis United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.MethodsRSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.ResultsEnrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses.ConclusionsBoth vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.Clinical trials registrationNCT03227029 and NCT03422237.

Copyright of Enfermería Neonatal is the property of Fundacion para la Salud Materno Infantil (FUNDASAMIN) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Patients living with chronic obstructive pulmonary disease (COPD) are at risk for lower respiratory tract infections caused by respiratory syncytial virus (RSV). The first RSV vaccines were approved in 2023 for adults ages 60 years and older. The safety and efficacy of the RSV vaccines and their clinical implications in patients living with COPD, apart from composite comorbidity results, are under-reported. Methods: This rapid review aimed to collect and report data pertaining to RSV vaccine safety and efficacy in patients living with COPD. Resources searched included Ovid MEDLINE, EMBASE, International Pharmaceutical Abstracts, published peer-reviewed abstracts, ClinicalTrials.gov, and the United States Food and Drug Administration (FDA) website. Results: Seven records were included: five research manuscripts and two ongoing clinical trials. Patients living with COPD were included in RSV vaccine clinical trials, but outcomes of RSV vaccine safety and efficacy in patients living with COPD were grossly unreported. Conclusions: Future clinical trials of patients living with COPD and subgroup analyses of patients living with COPD within existing studies evaluating RSV vaccine safety and efficacy are necessary to substantiate outcomes in this population. [ABSTRACT FROM AUTHOR]

IntroductionRespiratory syncytial virus (RSV) infection is one of the main causes of morbidity and mortality from lower respiratory tract infections in children under 5 years of age worldwide. Given that, the objective of this study was estimate the effectiveness of nirsevimab (a single-dose, long-acting, human recombinant monoclonal antibody against RSV) over time for the prevention of respiratory episodes treated at different levels of care.MethodsA prospective and dynamic population-based cohort study was performed including infants born between April 1 and December 31, 2023, in the Madrid region who resided there during the follow-up period from October 1, 2023, to February 29, 2024. Infants were considered immunized from the day after receiving one dose (50 or 100 mg) of nirsevimab or nonimmunized individuals if they did not receive any dose.ResultsThere were 4,100 episodes of primary care, 1,954 hospital emergencies, and 509 admissions, 82 of which required intensive care in the 33,859 participants analyzed. The adjusted effectiveness of nirsevimab in preventing hospitalization due to RSV infection was 93.6% (95% CI: 89.7 to 96.1) at 30 days and 87.6% (95% CI: 67.7 to 95.3) at 150 days. The number needed to treat to prevent one hospitalization were 314.19 (95% CI: 306.22 to 327.99) at 30 days and 24.30 (95% CI: 22.31 to 31.61) at 150 days. The adjusted effectiveness of nirsevimab in avoiding admission to an intensive care unit was 94.4% (95% CI: 87.3 to 97.5) at 30 days and 92.1% (95% CI: 64.0 to 98.3) at 90 days. The adjusted effectiveness of nirsevimab for avoiding primary care consultations and hospital emergency visits was lower.DiscussionImmunization with nirsevimab is an effective measure for reducing the burden of care related to RSV at all levels of care albeit it decreases throughout follow-up. At 150 days it remained high for preventing hospital admissions. Other articles already published have also demonstrated high effectiveness although with preliminary results, short follow-up periods and wide confidence intervals. None have detected a decrease in effectiveness over time. These results can be quite useful in individual infant prevention and in the design of immunization campaigns.

Background: Patients living with chronic obstructive pulmonary disease (COPD) are at risk for lower respiratory tract infections caused by respiratory syncytial virus (RSV). The first RSV vaccines were approved in 2023 for adults ages 60 years and older. The safety and efficacy of the RSV vaccines and their clinical implications in patients living with COPD, apart from composite comorbidity results, are under-reported. Methods: This rapid review aimed to collect and report data pertaining to RSV vaccine safety and efficacy in patients living with COPD. Resources searched included Ovid MEDLINE, EMBASE, International Pharmaceutical Abstracts, published peer-reviewed abstracts, ClinicalTrials.gov, and the United States Food and Drug Administration (FDA) website. Results: Seven records were included: five research manuscripts and two ongoing clinical trials. Patients living with COPD were included in RSV vaccine clinical trials, but outcomes of RSV vaccine safety and efficacy in patients living with COPD were grossly unreported. Conclusions: Future clinical trials of patients living with COPD and subgroup analyses of patients living with COPD within existing studies evaluating RSV vaccine safety and efficacy are necessary to substantiate outcomes in this population.

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of children, the elderly, and immunocompromised individuals. Currently, there are no FDA-approved RSV vaccines. The RSV G glycoprotein is used for viral attachment to host cells and impairment of host immunity by interacting with the human chemokine receptor CX3CR1. Antibodies that disrupt this interaction are protective against infection and disease. Nevertheless, development of an RSV G vaccine antigen has been hindered by its low immunogenicity and safety concerns. A previous study described three engineered RSV G proteins containing single-point mutations that induce higher levels of IgG antibodies and have improved safety profiles compared to wild-type RSV G (H. C. Bergeron, J. Murray, A. M. Nuñez Castrejon, et al., Viruses 13:352, 2021, https://doi.org/10.3390/v13020352). However, it is unclear if the mutations affect RSV G protein folding and display of its conformational epitopes. In this study, we show that the RSV G S177Q protein retains high-affinity binding to protective human and mouse monoclonal antibodies and has equal reactivity as wild-type RSV G protein to human reference immunoglobulin to RSV. Additionally, we determined the high-resolution crystal structure of RSV G S177Q protein in complex with the anti-RSV G antibody 3G12, further validating its antigenic structure. These studies show for the first time that an engineered RSV G protein with increased immunogenicity and safety retains conformational epitopes to high-affinity protective antibodies, supporting its further development as an RSV vaccine immunogen. IMPORTANCE Respiratory syncytial virus (RSV) causes severe lower respiratory diseases of children, the elderly, and immunocompromised populations. There currently are no FDA-approved RSV vaccines. Most vaccine development efforts have focused on the RSV F protein, and the field has generally overlooked the receptor-binding antigen RSV G due to its poor immunogenicity and safety concerns. However, single-point mutant RSV G proteins have been previously identified that have increased immunogenicity and safety. In this study, we investigate the antibody reactivities of three known RSV G mutant proteins. We show that one mutant RSV G protein retains high-affinity binding to protective monoclonal antibodies, is equally recognized by anti-RSV antibodies in human sera, and forms the same three-dimensional structure as the wild-type RSV G protein. Our study validates the structure-guided design of the RSV G protein as an RSV vaccine antigen.

SignificanceStrategies to reduce consumption of antimicrobial drugs are needed to contain the growing burden of antimicrobial resistance. Respiratory syncytial virus (RSV) is a prominent cause of upper and lower respiratory tract infections, as a single agent and in conjunction with bacterial pathogens, and may thus contribute to the burden of both inappropriately treated viral infections and appropriately treated polymicrobial infections involving bacteria. In a double-blind, randomized, placebo-controlled trial, administering an RSV vaccine to pregnant mothers reduced antimicrobial prescribing among their infants by 12.9% over the first 3 mo of life. Our findings implicate RSV as an important contributor to antimicrobial exposure among infants and demonstrate that this exposure is preventable by use of effective maternal vaccines against RSV.

Background: Respiratory syncytial virus (RSV) is garnering increasing attention, with a growing number of subunit RSV vaccines under active clinical investigation. However, comprehensive evidence is limited. Methods: We conducted a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov from database inception to 12 January 2024, focusing on published randomized controlled trials (RCTs). Results: A total of 17 studies were included, encompassing assessments of efficacy (5 studies), safety (17 studies), and immunogenicity (12 studies) of RSV subunit vaccines. The pooled risk ratio (RR) for RSV-associated acute respiratory infection (RSV-ARI) with subunit vaccines was 0.31 (95% CI: 0.23–0.43), for RSV-associated lower respiratory tract infection (RSV-LRTI), it was 0.32 (95% CI: 0.22–0.44), and for severe RSV-LRTI (RSV-SLRTI), it was 0.13 (95% CI: 0.06–0.29). There was no significant difference in serious adverse events (SAEs) between the vaccine and placebo groups, with a pooled RR of 1.05 (95% CI: 0.98–1.14). The pooled standardized mean difference (SMD) for the geometric mean titer (GMT) of neutralizing antibodies was 2.89 (95% CI: 2.43−3.35). Conclusion: Subunit RSV vaccines exhibit strong efficacy, favorable safety profiles, and robust immunogenicity. Future research should focus on the cost-effectiveness of various vaccines to enhance regional and national immunization strategies.

Respiratory syncytial virus (RSV) infection can cause bronchiolitis, pneumonia, morbidity, and some mortality, primarily in infants and the elderly, for which no vaccine is available. The RSV attachment (G) protein contains a central conserved domain (CCD) with a CX3C motif implicated in the induction of protective antibodies, thus vaccine candidates containing the G protein are of interest. This study determined if mutations in the G protein CCD would mediate immunogenicity while inducing G protein CX3C-CX3CR1 blocking antibodies. BALB/c mice were vaccinated with structurally-guided, rationally designed G proteins with CCD mutations. The results show that these G protein immunogens induce a substantial anti-G protein antibody response, and using serum IgG from the vaccinated mice, these antibodies are capable of blocking the RSV G protein CX3C-CX3CR1 binding while not interfering with CX3CL1, fractalkine.

Respiratory syncytial virus (RSV), an RNA virus spread by droplet infection that affects all ages, is increasingly recognised as an important pathogen in adults, especially among older people living with comorbidities. Distinguishing RSV from other acute viral infections on clinical grounds alone, with sufficient precision to be clinically useful, is not possible. The reference standard diagnosis is by PCR: point-of-care tests perform less well with lower viral loads. Testing samples from a single respiratory tract site could result in underdetection. RSV is identified in 6-11% of outpatient respiratory tract infection (RTI) consultations in older adults (≥60 years, or ≥65 years, depending on the study) and accounts for 4-11% of adults (≥18 years) hospitalised with RTI, with 6-15% of those hospitalised admitted to intensive care, and 1-12% of all adults hospitalised with RSV respiratory tract infection dying. Community-based studies estimate the yearly incidence of RSV infection at around 3-7% in adults aged 60 years and older in high-income countries. Although RSV accounts for a similar disease burden as influenza in adults, those hospitalised with severe RSV disease are typically older (most ≥60 years) and have more comorbidities, more respiratory symptoms, and are frequently without fever. Long-term sequelae are common and include deterioration of underlying disease (typically heart failure and COPD). There are few evidence-based RSV-specific treatments currently available, with supportive care being the main modality. Two protein subunit vaccines for protection from severe RSV in adults aged 60 years and older were licensed in 2023, and a third-an mRNA-based vaccine-recently gained market approval in the USA. The phase 3 studies in these three vaccines showed good protection against severe disease. Data on real-world vaccine effectiveness in older adults, including subgroups at high risk for RSV-associated hospitalisation, are needed to establish the best use of these newly approved RSV vaccines. New diagnostics and therapeutics are being developed, which will also need rigorous evaluation within their target populations to ensure they are used only for those in whom there is evidence of improved outcomes. There is an urgent need to reconceptualise this illness from one that is serious in children, but far less important than influenza in older people, to thinking of RSV as also a major risk to health for older people that needs targeted prevention and treatment., Competing Interests: Declaration of interests CCB contributed to an advisory board on RSV for Moderna; has received funding for prospective observational research on the epidemiology of RSV, and other viral infections in older people in primary care, through the European Clinical Research Alliance on Infectious Diseases from Sanofi; and was an investigator on the prospective observational RESCEU study of RSV in older adults, funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 116019. JGW has been an investigator for clinical trials funded by IMI/Horizon2020 and ZonMw, and clinical trials sponsored by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen. All funds have been paid to University Medical Centre Utrecht. JGW participated in advisory boards of Janssen and Sanofi, and was a speaker at a symposium sponsored by Sanofi, with honoraria paid to University Medical Centre Utrecht. DML has received personal fees from Gilead for an educational video, and from Merck for a roundtable discussion, speaker fees from Biotest, Takeda, and AstraZeneca, and support from Octapharma to attend a conference. DML also holds research grants from GlaxoSmithKline and Bristol Myers Squibb, and has received consultancy fees from GSK (paid to institution). JFS has undertaken consultancy for Adrenomed, Proveca, Clinsearch, and GARD-P, and has participated in a data safety and monitoring board for GlaxoSmithKline (all fees paid to institution)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI), hospital admission, and mortality in children worldwide. Early-life RSV LRTI has also been associated with subsequent long-term respiratory sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment, and these effects can persist into adulthood as chronic respiratory disease. New preventive measures (maternal vaccine or long-acting monoclonal antibodies) have been licensed to reduce the burden of acute RSV LRTI in infants and children at high risk through passive immunisation. Studies of these RSV prevention products show high efficacy and effectiveness, particularly for preventing severe RSV LRTI, with implementation in many high-income countries, but limited access in low-income and middle-income countries (LMICs). These interventions might also reduce the risk of additional health outcomes and long-term morbidity. This Series paper provides the evidence for the long-term effects of early-life RSV disease, discusses mechanisms of disease development, and addresses the potential full public health value of prevention of RSV illness. Further research is needed to determine whether prevention of RSV LRTI or delay of RSV illness in early life might prevent or ameliorate the development of associated long-term respiratory disease. This potential further underscores the urgency for access and availability of new interventions to prevent early-life RSV LRTI in LMICs., Competing Interests: Declaration of interests HJZ is supported by the South African Medical Research Council; reports grants from AstraZeneca, Merck, and Pfizer for trials of RSV prevention and from the Gates Foundation for studies in childhood pneumonia (including RSV); has served on advisory boards of Merck and Pfizer on RSV prevention; has received speaker fees from Pfizer; serves on a data safety monitoring board for Moderna outside of the submitted work; and has served on the WHO Technical Advisory Group on new RSV preventive interventions. FC is supported by a National Institutes of Health (NIH) grant (NIH T32 ES007028). AM reports funding support from NIH, Merck, and Jansen; has served on advisory boards for Merck, Pfizer, Sanofi-Pasteur, AstraZeneca, Enanta, and Moderna outside of the submitted work; and has received speaker fees and travel and meeting support from Pfizer and Sanofi-Pasteur for educational lectures. RTS reports having received honoraria for advisory board meetings and pharma-sponsored symposia from Pfizer, Sanofi, Moderna, AstraZeneca, and OM-Pharma. TVH reports grants from the NIH; fees from the American Thoracic Society, the Parker B Francis Council of Scientific Advisors, and the NIH National Health Lung and Blood Institute for serving on council, and from Pfizer for serving on vaccine data safety monitoring boards; and speaker fees for invited talks from the American Academy of Allergy, Asthma and Immunology, and for an invited respiratory forum from Sanofi outside of the submitted work. JRO reports grants from the NIH and The Vaccine Company for research support and for participation on a data safety monitoring board. JRO is on scientific advisory boards for GSK, Moderna, and Pfizer. He has received personal funding from the France Foundation to develop RSV-continuing medical education materials. His institution has received RSV research funds from the Bill & Melinda Gates Foundation and the World Health Organization. TK declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Respiratory syncytial virus (RSV) is a leading cause of respiratory illness in infants globally, with new maternal RSV vaccines on the horizon. Vaccine decision-making during pregnancy is shaped by individual, interpersonal, community, and societal factors. This study explored key interpersonal influences on maternal vaccine decision-making among pregnant and lactating people (PLP) and community members in Kenya., Methods: This qualitative study conducted in-depth interviews with six pregnant people, 18 lactating people, and 10 community members in one rural and one urban county in Kenya. Data were analyzed using a grounded theory approach., Results: Participants identified the pregnant person themself, male partners, other family members, peers, and healthcare providers (HCPs) as key influences on the maternal immunization decision-making process. The majority of interviewed PLP believed that decision-making during pregnancy should be left to themselves due to autonomy and their role as the primary caregiver. Community members, including male partners, also identified pregnant people as the key decision-maker. While some PLP said they deferred to male partners to make vaccine decisions, more felt that men were not as informed on maternal and child issues as themselves or other female peers and relatives. HCPs emerged as important influences and information sources for PLP during decision-making., Discussion: Understanding who influences vaccine-decision making during pregnancy will help inform demand generation strategies, and in turn, uptake of future maternal vaccines, including RSV vaccines. Given the strong role HCPs and peers have in the decision-making process, targeting key potential influences is essential to improve vaccine acceptance., (© 2024. The Author(s).)

We investigated the uptake of nirsevimab for infants and the bivalent respiratory syncytial virus prefusion F (RSVPreF) vaccine for pregnant persons as measures for RSV prevention during an infant's birth hospitalization in a military treatment facility. We found >85% uptake between October 2023 to February 2024. These data may aid health systems plan for future RSV seasons., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Published by Elsevier Inc.)

Competing Interests: Competing interests:: Bahaa Abu-Raya reports honoraria for participation in meetings from Sanofi, and is coinvestigator on studies funded by GSK, Pfizer, Merck, Moderna, Vaccitech, and Inventprise. Joanne Langley reports funding for clinical trials from GSK, Pfizer, Merck, Moderna, Sanofi, and Sequris, paid to Dalhousie University; consulting fees from GSK, Sanofi, Enanta, and Sequris, paid to departmental academic funds; and travel support from Sanofi, Enanta, and Sequris. She reports participation on a data safety monitoring board for a pneumococcal vaccine trial with Vaxcyte and the SNAP trial. She is medical advisor for the Nova Scotia Palivizumab for RSV Prevention Program and a member of a working group on influenza with the National Advisory Committee on Immunization. Pascal Lavoie is medical director of the British Columbia RSV Immunoprophylaxis Program and is employed by the Provincial Health Services Authority of British Columbia. He received honoraria for participating in an advisory board for Sanofi Canada. No other competing interests were declared.

The global burden of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children is high. The RSV prevention strategies approved in 2023 will be essential to lowering the global disease burden. In this Series paper, we describe clinical presentation, burden of disease, hospital management, emerging therapies, and targeted prevention focusing on developments and groundbreaking publications for RSV. We conducted a systematic search for literature published in the past 15 years and used a non-systematic approach to analyse the results, prioritising important papers and the most recent reviews per subtopic. Annually, 33 million episodes of RSV LRTI occur in children younger than 5 years, resulting in 3·6 million hospitalisations and 118 200 deaths. RSV LRTI is a clinical diagnosis but a clinical case definition and universal clinical tool to predict severe disease are non-existent. The advent of molecular point-of-care testing allows rapid and accurate confirmation of RSV infection and could reduce antibiotic use. There is no evidence-based treatment of RSV, only supportive care. Despite widespread use, evidence for high-flow nasal cannula (HFNC) therapy is insufficient and increased paediatric intensive care admissions and intubation indicate the need to remove HFNC therapy from standard care. RSV is now a vaccine-preventable disease in young children with a market-approved long-acting monoclonal antibody and a maternal vaccine targeting the RSV prefusion protein. To have a high impact on life-threatening RSV infection, infants at high risk, especially in low-income and middle-income countries, should be prioritised as an interim strategy towards universal immunisation. The implementation of RSV preventive strategies will clarify the full burden of RSV infection. Vaccine probe studies can address existing knowledge gaps including the effect of RSV prevention on transmission dynamics, antibiotic misuse, the respiratory microbiome composition, and long-term sequalae., Competing Interests: Declaration of interests NIM report grants from the Gates Medical Research Institute, the Dutch Lung Foundation, and the Bill & Melinda Gates Foundation; consulting and speaker fees have been paid to the University Medical Center Utrecht for Abbvie, Medimmune, Sanofi, and Merck; and ReSVinet and the Bill & Melinda Gates Foundation have provided support for NIM for attending meetings. MCN reports grants from the Bill & Melinda Gates Foundation, European & Developing Countries Clinical Trials Partnership, Pfizer, AstraZeneca, and Sanofi and personal fees from Pfizer and Sanofi. MTC reports grants from the Bill & Melinda Gates Foundation, and personal fees from Sanofi, outside the submitted work., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: Competing interests:: Elissa Abrams is a board member of the Canadian Society of Allergy and Clinical Immunology and president of the Allergy Section of the Canadian Paediatric Society. No other competing interests were declared.

Respiratory syncytial virus (RSV) is a threat to infants globally causing bronchiolitis and pneumonia. Despite decades of research, RSV outbreaks occur with only modest advancements in prevention or treatment. Vaccine development faced challenges because past attempts caused enhanced disease and treatment options demonstrated limited efficacy. Recent advancements, including maternal vaccines focusing on the prefusion form of the F glycoprotein are now showing significant benefits in preventing severe RSV-related illness in infants. Additionally, monoclonal antibodies offer prevention directly to newborns within 1 week of birth. These innovations have the potential to substantially change the impact of RSV., (Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.)

Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infections, among others. However, many gaps in knowledge regarding the immunobiology of maternal immunisation prevent the optimal design and application of this successful public health intervention. Therefore, we did an innovative landscape analysis to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop that gathered experts across several maternal immunisation initiatives-group B streptococcus, respiratory syncytial virus, pertussis, and influenza. Finally, a global online survey prioritised the identified knowledge gaps on the basis of expert opinion about their importance and relevance. Here we present the results of this worldwide landscape analysis and discuss the identified research gaps.

Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK's Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro . These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro .

Our study aims to assess the public's perceptions of respiratory syncytial virus (RSV) and attitudes toward the RSV vaccine and to identify associated factors in China. A nationwide cross-sectional survey conducted using an online platform between August 16 and September 14, 2023. Questions related to socio-demographics, awareness, knowledge, perceptions of susceptibility and severity of RSV, and attitudes toward the RSV vaccine were included in the questionnaire. We used the chi-square test and logistic regression model to explore the associated factors. Overall, 2133 individuals were included in this study. Nearly a quarter of participants (24.3%) indicated that they had never heard of RSV. The proportion of individuals aged over 50 years reporting never having heard of RSV (36.5%) and having a low knowledge level of RSV (55.3%) was significantly higher that of other younger age groups. More than half of individuals (55.7%) exhibited low level of perceptions of susceptibility concerning RSV infection. A total of 68.4% of the participants expressed willingness to receive the RSV vaccine. Younger age was positively associated with a higher willingness to be vaccinated. The most frequent reason for declining the vaccine was "Concern about vaccine's safety or side effects." About 60% of individuals considered a price of RSV vaccine below 200 CNY (28 USD) as acceptable. The awareness and perceived susceptibility to RSV infection were limited to the Chinese public. It is necessary to take measures to address the low awareness and knowledge of RSV and acceptability of the RSV vaccine among older adults.

Introduction: Respiratory syncytial virus (RSV) infection is one of the main causes of morbidity and mortality from lower respiratory tract infections in children under 5 years of age worldwide. Given that, the objective of this study was estimate the effectiveness of nirsevimab (a single-dose, long-acting, human recombinant monoclonal antibody against RSV) over time for the prevention of respiratory episodes treated at different levels of care., Methods: A prospective and dynamic population-based cohort study was performed including infants born between April 1 and December 31, 2023, in the Madrid region who resided there during the follow-up period from October 1, 2023, to February 29, 2024. Infants were considered immunized from the day after receiving one dose (50 or 100 mg) of nirsevimab or nonimmunized individuals if they did not receive any dose., Results: There were 4,100 episodes of primary care, 1,954 hospital emergencies, and 509 admissions, 82 of which required intensive care in the 33,859 participants analyzed. The adjusted effectiveness of nirsevimab in preventing hospitalization due to RSV infection was 93.6% (95% CI: 89.7 to 96.1) at 30 days and 87.6% (95% CI: 67.7 to 95.3) at 150 days. The number needed to treat to prevent one hospitalization were 314.19 (95% CI: 306.22 to 327.99) at 30 days and 24.30 (95% CI: 22.31 to 31.61) at 150 days. The adjusted effectiveness of nirsevimab in avoiding admission to an intensive care unit was 94.4% (95% CI: 87.3 to 97.5) at 30  days and 92.1% (95% CI: 64.0 to 98.3) at 90 days. The adjusted effectiveness of nirsevimab for avoiding primary care consultations and hospital emergency visits was lower., Discussion: Immunization with nirsevimab is an effective measure for reducing the burden of care related to RSV at all levels of care albeit it decreases throughout follow-up. At 150 days it remained high for preventing hospital admissions. Other articles already published have also demonstrated high effectiveness although with preliminary results, short follow-up periods and wide confidence intervals. None have detected a decrease in effectiveness over time. These results can be quite useful in individual infant prevention and in the design of immunization campaigns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barbas Del Buey, Íñigo Martínez, Gutiérrez Rodríguez, Alonso García, Sánchez-Gómez, Lasheras Carbajo, Jiménez Bueno, Esteban Vasallo, López Zambrano, Calvo Rey, Sanchez Luna, Molina Olivas and Arce Arnáez.)

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leszek Szenborn reports a relationship with GSK that includes: speaking and lecture fees. Leszek Szenborn reports a relationship with Sanofi that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier India Pvt Ltd. All rights reserved.)

Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development. We also discuss the challenges associated with vaccine production in CHO cells, with a focus on ensuring viral clearance for eVLP products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immunized with G proteins from RSV-A2 and RSV-B1 strains. These monoclonal antibodies recognize six unique antigenic classes (G0-G5). None of the anti-G monoclonal antibodies neutralize RSV-A2 or RSV-B1 in vitro. In mice challenged with either RSV-A2 line 19 F or RSV-B1, one day after treatment with anti-G monoclonal antibodies, all monoclonal antibodies reduce lung pathology and significantly reduce lung infectious viral titers by more than 2 logs on day 5 post-RSV challenge. RSV dissemination in the lungs was variable and correlated with lung pathology. We demonstrate new cross-protective anti-G monoclonal antibodies targeting multiple sites including conformation-dependent class G0 MAb 77D2, CCD-specific class G1 MAb 40D8, and carboxy terminus of CCD class G5 MAb 7H11, to support development of G-targeting monoclonal antibodies against RSV., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)