Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Balanced on the Biggest Wave: Nirsevimab for Newborns.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.

An epidemiological investigation of high-risk infants for Respiratory Syncytial Virus infections: a retrospective cohort study.

BACKGROUND: Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context. METHODS: This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described. RESULTS: A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use. CONCLUSIONS: The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.

Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana.

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.

Management and outcomes of bronchiolitis in Italy and Latin America: a multi-center, prospective, observational study.

We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons.  This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form.  Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy. CONCLUSIONS: We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world. WHAT IS KNOWN: • Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world. WHAT IS NEW: • There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

Exploratory analysis of the economically justifiable price of nirsevimab for healthy late-preterm and term infants in Colombia.

INTRODUCTION: Respiratory syncytial virus infection is the leading cause of lower respiratory infection globally. Recently, nirsevimab has been approved to prevent respiratory syncytial virus (RSV) infection. This study explores the economically justifiable price of nirsevimab for preventing RSV infection in Colombia's children under 1 year of age. MATERIALS AND METHODS: A static model was developed using the decision tree microsimulation to estimate the quality-adjusted costs and life years of two interventions: a single intramuscular dose of nirsevimab versus not applying nirsevimab. This analysis was made during a time horizon of 1 year and from a societal perspective. RESULTS: The annual savings in Colombia associated with this cost per dose ranged from U$ 2.5 to 4.1 million. Based on thresholds of U$ 4828, U$ 5128, and U$ 19 992 per QALY evaluated in this study, we established economically justifiable drug acquisition prices of U$ 21.88, U$ 25.04, and U$ 44.02 per dose of nirsevimab. CONCLUSION: the economically justifiable cost for nirsevimab in Colombia is between U$ 21 to U$ 44 per dose, depending on the willingness to pay used to decide its implementation. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

Clinical, Genomic, and Immunological Characterization of RSV Surge in Sydney, Australia, 2022.

OBJECTIVES: The 2022 seasonal respiratory syncytial virus (RSV) epidemic in Sydney, Australia saw an unprecedented number of RSV detections. We aimed to characterize genomic and immunologic factors associated with the surge in RSV cases. METHODS: Whole genome sequences of RSV were generated from 264 RSV-infected infants and linked to case-matched clinical data from the 2022 southern hemisphere RSV season. We then performed an immunologic analysis of baseline RSV-specific humoral immunity in women of childbearing age before and throughout the coronavirus disease 2019 pandemic. RESULTS: Clinical analysis revealed a high burden of disease across patients of all health backgrounds. More than one-half of RSV-related health care visits by infants resulted in hospitalization, and one-quarter required high-flow respiratory support or a higher level of care. Viral phylogenetic analyses revealed that 2022 Sydney RSV sequences were closely related to viruses that had been circulating globally since 2017, including those detected in recent US outbreaks. Nonsynonymous mutations within the palivizumab and nirsevimab binding sites were detected at low frequencies. There was no difference in baseline RSV-neutralizing antibody titers between 2020 and 2022. CONCLUSIONS: Collectively, these findings suggest that neither the emergence of a novel RSV genotype nor hypothesized immune debt was associated with the surge of RSV cases and hospitalizations in 2022. Continued genomic and immunologic surveillance is required to further understand the factors driving outbreaks of RSV globally, and to inform guidelines for the rollout and ongoing use of recently developed immunotherapeutics and vaccines.

Palivizumab en niños nacidos de 35 semanas o menos de gestación y menores de 6 meses de edad al inicio de la estación de riesgo de infección por virus sincitial respiratorio / Palivizumab in children born at 35 weeks or less of gestation and children under 6 months of age at the beginning of the season at risk for respiratory syncytial virus infection

INTRODUCCIÓN: Este informe de ETS-R se realizó a solicitud de la Dirección General de Intervenciones Estratégicas en Salud Pública del Ministerio de Salud (DGIESP / MINSA); la cual motivó la formulación de una pregunta PICO conjuntamente con representantes tanto de la Dirección de Intervenciones por Curso de Vida y Cuidado Integral de la DGIESP como del Centro de Evaluación de Tecnologías en Salud (CETS) del Instituto Nacional de Salud. La pregunta PICO formulada fue la siguiente: P: pacientes pediátricos con alto riesgo de enfermedad por virus sincitial respiratorio (VSR); I: palivizumab; C: placebo o no administración; O: mortalidad, hospitalización por VSR, eventos adversos y calidad de vida. Para la presente evaluación, se consideró la primera categoría de alto riesgo de la ficha técnica DIGEMID, que corresponde a la población de recién nacidos de 35 semanas o menos de gestación y menores de 6 meses de edad al inicio de la estación de riesgo de infección por VSR. No se consideró población pediátrica con comorbilidades asociadas, como enfermedad pulmonar crónica, displasia broncopulmonar o cardiopatía congénita. OBJETIVOS: Describir la evidencia científica disponible sobre la eficacia y seguridad de la Inmunoglobulina Intravenosa (IgIV) para el tratamiento de encefalitis autoinmune en pacientes pediátricos que no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline/PubMed, The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados (ECA), revisiones sistemáticas (RS) de ECA, estudios observacionales comparativos, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando: AMSTAR 2 para revisiones sistemáticas, la herramienta de la colaboración Cochrane para ensayos clínicos, la escala Newcastle-Ottawa para estudios no aleatorizados incluyendo cohortes y estudios de casos y controles, y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Tras la búsqueda sistemática se identificaron 207 artículos de los cuales 11 pararon a revisión a texto completo. De estos 11 documentos solo uno (GPC) correspondió con la pregunta PICO de interés. No se identificaron ECA o estudios observacionales comparativos, evaluaciones económicas, ni ETS que respondieran a la pregunta PICO de interés. CONCLUSIONES: Se revisó la mejor evidencia disponible sobre la eficacia y seguridad de la IgIV más metilprednisolona en pacientes pediátricos con encefalopatía autoinmune no mejoran con respuesta a pulsos de metilprednisolona y/o plasmaféresis (población objetivo). Se identificó solo una GPC que brinda recomendaciones para la población objetivo basada únicamente en consenso de expertos. Esta guía recomienda tanto la intervención como el comparador (prolongar el uso de metilprednisolona). No se cuenta con evidencia procedente de estudios tipo ECA u observacionales comparativos que evalúen la eficacia y seguridad de IgIV más metilprednisolona en la población objetivo, incluso ni en el contexto de primera línea. No se disponen de ETS ni evaluaciones económicas que respondan a la pregunta PICO de la presente revisión. Se espera que los resultados de ensayos clínicos en curso puedan brindar nueva información que permita responder a la pregunta de la presente revisión.

Efficacy of Palivizumab Immunoprophylaxis for Reducing Severe RSV Outcomes in Children with Immunodeficiencies: A Systematic Review.

BACKGROUND: Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care. OBJECTIVE: To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children. METHODS: We searched Ovid MEDLINE and EMBASE for published clinical studies that investigated outcomes of palivizumab use in children. We included clinical trials, cohort studies, and case-control studies. The primary outcomes were RSV-related or respiratory viral infection-related hospitalizations, or RSV-related mortality. This systematic review was registered in PROSPERO (ID CRD42021248619) and is reported in accordance with the PRISMA guidelines. RESULTS: From the 1993 records, six studies were eligible and included, for a total of 625 immunocompromised children with an heterogeneous composition of primary and acquired immunodeficiencies enrolled from palivizumab programs. There were no intervention studies. None of the studies included a control group. RSV hospitalizations were infrequent (0%-3.1% of children). Most children included received palivizumab, although one study (n = 56) did not specify how many received palivizumab. RSV mortality was neither observed, in three studies, nor reported, in three other studies. CONCLUSIONS: The evidence supporting the use of palivizumab for prevention of severe RSV disease in immunocompromised children remains extremely limited and appears insufficient to justify prioritizing this intervention as the current standard of care over alternative interventions.

Inhaled "Muco-Trapping" Monoclonal Antibody Effectively Treats Established Respiratory Syncytial Virus (RSV) Infections.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable "muco-trapping" variant of motavizumab (Mota-MT), a potent neutralizing mAb against RSV F is engineered. Mota-MT traps RSV in AM via polyvalent Fc-mucin bonds, reducing the fraction of fast-moving RSV particles in both fresh pediatric and adult AM by ≈20-30-fold in a Fc-glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota-MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota-MT to RSV-infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000-fold and 100 000-fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota-MT-treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco-trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.

Nirsevimab Immunization to Prevent Respiratory Syncytial Virus-Associated Lower Respiratory Tract Infections in Infants and Children up to 24 Months of Age.

Respiratory syncytial virus (RSV) infects nearly all infants in their first year of life and is the leading cause of hospitalization for infants younger than 1 year of age in the United States. Historically, the only option for RSV prevention was palivizumab. However, not all infants are eligible for palivizumab, it requires multiple doses per RSV season, and it is costly. In July 2023, the U.S. Food and Drug Administration approved nirsevimab for the prevention of RSV-associated lower respiratory tract infections for all infants. Nirsevimab inhibits RSV from fusing to cellular membranes and thereby neutralizes the virus in the body. Nirsevimab is expected to significantly reduce the health and economic burdens of RSV. This article provides an overview of nirsevimab, potential adverse effects, and implications for nursing practice.

Cost-effectiveness of nirsevimab and palivizumab for respiratory syncytial virus prophylaxis in preterm infants 29-34 6/7 weeks' gestation in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) hospitalizations have increased since the 2014 guideline update recommended against the use of palivizumab for preterm infants born ≥29 0/7 weeks' gestational age (GA) without additional risk factors. A novel drug candidate, nirsevimab, has been developed for this population. We analyzed the cost-effectiveness of palivizumab/nirsevimab vs. no prophylaxis in this population. METHODS: A hybrid-Markov model predicted the RSV clinical course in the first year of life and sequelae in the subsequent four years for preterm infants from the healthcare and societal perspectives. Model parameters were derived from the literature. We calculated costs and quality-adjusted life-years (QALYs) to produce an incremental cost-effectiveness ratio (ICER) evaluated at a willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses assessed model robustness. A threshold analysis examined nirsevimab pricing uncertainty. RESULTS: Compared to no prophylaxis, palivizumab costs $9572 and $9584 more from the healthcare and societal perspectives, respectively, with 0.0019 QALYs gained per patient over five years, resulting in ICERs >$5 million per QALY from each perspective. Results were robust to parameter uncertainties; probabilistic sensitivity analysis revealed that no prophylaxis had a 100% probability of being cost-effective. The threshold analysis suggested that nirsevimab is not cost-effective when compared to no prophylaxis if the price exceeds $1962 from a societal perspective. CONCLUSION: Palivizumab is dominated by no prophylaxis for preterm infants 29 0/7-34 6/7 weeks' GA with no additional risk factors. Relevant stakeholders should consider alternatives to palivizumab for this population that are both effective and economical.

Society for Maternal-Fetal Medicine Statement: Clinical considerations for the prevention of respiratory syncytial virus disease in infants.

Respiratory syncytial virus is a leading cause of lower respiratory tract illness globally in children aged <5 years. Each year, approximately 58,000 hospitalizations in the United States are attributed to respiratory syncytial virus. Infants aged ≤6 months experience the most severe morbidity and mortality. Until recently, prevention with the monoclonal antibody, palivizumab, was only offered to infants with high-risk conditions, and treatment primarily consisted of supportive care. Currently, 2 products are approved for the prevention of respiratory syncytial virus in infants. These include the Pfizer bivalent recombinant respiratory syncytial virus prefusion F protein subunit vaccine, administered seasonally to the pregnant person between 32 0/7 and 36 6/7 weeks of gestation, and the monoclonal antibody, nirsevimab, administered to infants aged up to 8 months entering their first respiratory syncytial virus season. With few exceptions, administering both the vaccine to the pregnant person and the monoclonal antibody to the infant is not recommended. All infants should be protected against respiratory syncytial virus using one of these strategies. Key considerations for pregnant individuals include examining available safety and efficacy data, weighing accessibility and availability, and patient preferences for maternal vaccination vs infant monoclonal antibody treatment. It will be critical for maternal-fetal medicine physicians to provide effective and balanced counseling to aid patients in deciding on a personalized approach to the prevention of respiratory syncytial virus in their infants.

Approaches to the Prevention and Treatment of Respiratory Syncytial Virus Infection in Children: Rationale and Progress to Date.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, and is associated with long-term pulmonary sequelae for up to 30 years after infection. The mainstay of RSV management is supportive therapy such as supplemental oxygen. Palivizumab (Synagis™-AstraZeneca), a monoclonal antibody targeting the RSV F protein site II, has been licensed for the prevention of RSV in high-risk groups since 1998. There has been recent promising progress in preventative strategies that include vaccines and long-acting, high-potency monoclonal antibodies. Nirsevimab (Beyfortus™-AstraZeneca/Sanofi), a monoclonal antibody with an extended half-life, has recently been registered in the European Union and granted licensure by the US Food and Drug Administration. Furthermore, a pre-fusion sub-unit protein vaccine has been granted licensure for pregnant women, aimed at protecting their young infants, following established safety and efficacy in clinical trials (Abrysvo™-Pfizer). Also, multiple novel antiviral therapeutic options are in early phase clinical trials. The next few years have the potential to change the landscape of LRTI through improvements in the prevention and management of RSV LRTI. Here, we discuss these new approaches, current research, and clinical trials in novel therapeutics, monoclonal antibodies, and vaccines against RSV infection in infants and children.

A molecular perspective for the development of antibodies against the human respiratory syncytial virus.

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.

Palivizumab prophylaxis in preterm infants and subsequent wheezing/asthma: 10-year follow-up study.

BACKGROUND: Respiratory syncytial virus (RSV) causes not only infantile recurrent wheezing but also the development of asthma. To investigate whether palivizumab, an anti-RSV monoclonal antibody, prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing and/or development of asthma, at 10 years of age. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 6 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice (SCELIA study). Here, we followed these subjects until 10 years of age. Parents of study subjects reported the patients' physician's assessment of recurrent wheezing/asthma, using a report card and a novel mobile phone-based reporting system using the internet. The relationship between RSV infection and asthma development, as well as the relationship between other factors and asthma development, were investigated. RESULTS: Of 154 preterm infants enrolled, 113 received palivizumab during the first year of life. At 10 years, although both recurrent wheezing and development of asthma were not significantly different between the treated and untreated groups, maternal smoking with aeroallergen sensitization of the patients was significantly correlated with physician-diagnosed asthma. CONCLUSIONS: In contrast to the prior study results at 6 years, by 10 years palivizumab prophylaxis had no impact on recurrent wheezing or asthma, but there was a significant correlation between maternal passive smoking with aeroallergen sensitization and development of asthma by 10 years of age.

Early lessons from the implementation of universal respiratory syncytial virus prophylaxis in infants with long-acting monoclonal antibodies, Galicia, Spain, September and October 2023.

A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries' programmatic deliberations.