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Anales de Pediatria Oct 2023Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. (Review)
Review
INTRODUCTION
Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.
OBJECTIVES
To provide recommendations for the administration of nirsevimab for prevention of RSV disease.
METHODS
The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions.
RESULTS
In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis.
CONCLUSIONS
Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.
Topics: Infant, Newborn; Infant; Humans; Child; Antiviral Agents; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Communicable Diseases; Respiratory Tract Infections; Bronchiolitis
PubMed: 37743207
DOI: 10.1016/j.anpede.2023.09.006 -
The Journal of Biological Chemistry Nov 2023Synthetic cytokine receptors can modulate cellular functions based on an artificial ligand to avoid off-target and/or unspecific effects. However, ligands that can...
Synthetic cytokine receptors can modulate cellular functions based on an artificial ligand to avoid off-target and/or unspecific effects. However, ligands that can modulate receptor activity so far have not been used clinically because of unknown toxicity and immunity against the ligands. Here, we developed a fully synthetic cytokine/cytokine receptor pair based on the antigen-binding domain of the respiratory syncytial virus-approved mAb Palivizumab as a synthetic cytokine and a set of anti-idiotype nanobodies (AIP) as synthetic receptors. Importantly, Palivizumab is neither cross-reactive with human proteins nor immunogenic. For the synthetic receptors, AIP were fused to the activating interleukin-6 cytokine receptor gp130 and the apoptosis-inducing receptor Fas. We found that the synthetic cytokine receptor AIPgp130 was efficiently activated by dimeric Palivizumab single-chain variable fragments. In summary, we created an in vitro nonimmunogenic full-synthetic cytokine/cytokine receptor pair as a proof of concept for future in vivo therapeutic strategies utilizing nonphysiological targets during immunotherapy.
Topics: Humans; Palivizumab; Receptors, Artificial; Receptors, Cytokine; Cytokines; Respiratory Syncytial Virus Infections; Ligands; Respiratory Syncytial Virus, Human; Antiviral Agents
PubMed: 37734558
DOI: 10.1016/j.jbc.2023.105270 -
Drug, Healthcare and Patient Safety 2023Respiratory Syncytial Virus (RSV) is a major global cause of childhood morbidity and mortality. Palivizumab, a monoclonal antibody that provides passive immunity against... (Review)
Review
Respiratory Syncytial Virus (RSV) is a major global cause of childhood morbidity and mortality. Palivizumab, a monoclonal antibody that provides passive immunity against RSV, is currently licensed for prophylactic use in specific "high-risk" populations, including congenital heart disease, bronchopulmonary dysplasia and prematurity. Available research suggests palivizumab use in these high-risk populations can lead to a reduction in RSV-related hospitalization. However, palivizumab has not been demonstrated to reduce mortality, adverse events or length of hospital stay related to RSV. In this article, we review the management of RSV, indications for palivizumab prophylaxis, the safety, cost-effectiveness and efficacy of this preventative medication, and emerging therapeutics that could revolutionize future prevention of this significant pathogen.
PubMed: 37720805
DOI: 10.2147/DHPS.S348727 -
The Medical Letter on Drugs and... Sep 2023
Topics: Child; Child, Preschool; Humans; Antibodies, Monoclonal, Humanized
PubMed: 37682698
DOI: 10.58347/tml.2023.1685a -
Pediatrics Nov 2023
Topics: Humans; Palivizumab; Antiviral Agents; Vaccines
PubMed: 37682622
DOI: 10.1542/peds.2023-063817 -
Journal of the Pediatric Infectious... Sep 2023Severe respiratory syncytial virus (RSV) infections disparately impact American Indian communities. We implemented a program that expanded palivizumab to all children...
Severe respiratory syncytial virus (RSV) infections disparately impact American Indian communities. We implemented a program that expanded palivizumab to all children under 2 years of age that led to significant reductions in RSV infections and hospitalizations for both high-risk and non-high-risk recipients in a rural American Indian community in Eastern Arizona.
PubMed: 37671822
DOI: 10.1093/jpids/piad063 -
Neonatal Network : NN Aug 2023Respiratory syncytial virus (RSV) is a leading cause of morbidity and hospitalization in young children, and prevention is the primary management strategy. At present,...
Understanding Policy Decisions and Their Implications Regarding Preventive Interventions for Respiratory Syncytial Virus (RSV) Infection in Canadian Infants: A Primer for Nurses.
Respiratory syncytial virus (RSV) is a leading cause of morbidity and hospitalization in young children, and prevention is the primary management strategy. At present, palivizumab, a monoclonal antibody providing immediate passive immunity, rather than a vaccine that induces active immunity, is the only preventive intervention used in routine practice internationally. In Canada, access varies across the country. Prophylaxis policies are mainly driven by cost-effectiveness analyses, and it is crucial that the full costs and benefits of any intervention are captured. Positive results from a new Canadian cost-effectiveness analysis of palivizumab will help address the current inequality in use while providing a framework for future models of RSV preventives. Nurses are the principal educators for parents about the risks of childhood RSV and optimal prevention basic hygiene, behavioral and environmental measures, and seasonal prophylaxis. Nurses should be provided not only with regular, up-to-date, and accurate information on RSV and the clinical aspects of emerging interventions but be informed on the decision-making governing the use of preventive strategies.
PubMed: 37657806
DOI: 10.1891/NN-2023-0005 -
PloS One 2023Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool...
A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.
Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.
Topics: Infant, Newborn; Infant; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Gestational Age; Antiviral Agents; Infant, Premature; Antibodies, Monoclonal, Humanized; Risk Factors; Respiratory Syncytial Virus, Human; Hospitalization; Italy
PubMed: 37561741
DOI: 10.1371/journal.pone.0289828 -
Protein Engineering, Design & Selection... Jan 2023Monoclonal antibody (mAb) therapies have rapidly become a powerful class of therapeutics with applications covering a diverse range of clinical indications. Though most...
Monoclonal antibody (mAb) therapies have rapidly become a powerful class of therapeutics with applications covering a diverse range of clinical indications. Though most widely used for the treatment of cancer, mAbs are also playing an increasing role in the defense of viral infections, most recently with palivizumab for prevention and treatment of severe RSV infections in neonatal and pediatric populations. In addition, during the COVID-19 pandemic, mAbs provided a bridge to the rollout of vaccines; however, their continued role as a therapeutic option for those at greatest risk of severe disease has become limited due to the emergence of neutralization resistant Omicron variants. Although there are many techniques for the identification of mAbs, including single B cell cloning and immunization of genetically engineered mice, the low cost, rapid throughput and technological simplicity of antibody phage display has led to its widespread adoption in mAb discovery efforts. Here we used our 27-billion-member naïve single-chain antibody (scFv) phage library to identify a panel of neutralizing anti-SARS-CoV-2 scFvs targeting diverse epitopes on the receptor binding domain (RBD). Although typically a routine process, we found that upon conversion to IgG, a number of our most potent clones failed to maintain their neutralization potency. Kinetic measurements confirmed similar affinity to the RBD; however, mechanistic studies provide evidence that the loss of neutralization is a result of structural limitations likely arising from initial choice of panning antigen. Thus this work highlights a risk of scFv-phage panning to mAb conversion and the importance of initial antigen selection.
Topics: Animals; Mice; Humans; Epitopes; Single-Chain Antibodies; Pandemics; SARS-CoV-2; COVID-19; Antibodies, Viral; Antibodies, Monoclonal; Immunoglobulin G; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing
PubMed: 37561410
DOI: 10.1093/protein/gzad008 -
The Lancet Regional Health. Western... Oct 2023Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV...
Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial.
BACKGROUND
Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan.
METHODS
This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days.
FINDINGS
Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period.
INTERPRETATION
Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study.
FUNDING
Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.
PubMed: 37554997
DOI: 10.1016/j.lanwpc.2023.100847