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Human Vaccines & Immunotherapeutics Dec 2024Respiratory 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 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 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 . These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV .
Topics: Infant; Animals; Humans; Infant, Newborn; Aged; Palivizumab; Nicotiana; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Antibodies, Viral; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Viral Fusion Proteins; Respiratory Syncytial Virus Vaccines; Mammals
PubMed: 38508690
DOI: 10.1080/21645515.2024.2327142 -
Pediatrics Nov 2023
Topics: Humans; Palivizumab; Antiviral Agents; Vaccines
PubMed: 37682622
DOI: 10.1542/peds.2023-063817 -
Human Vaccines & Immunotherapeutics Dec 2024Nirsevimab 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....
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.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Hospitalization; Antiviral Agents; Respiratory Syncytial Virus, Human; Female; Male; Respiratory Tract Infections; Immunization Programs; Infant, Newborn; Child, Preschool; Palivizumab; Antibodies, Monoclonal, Humanized
PubMed: 38738683
DOI: 10.1080/21645515.2024.2348135 -
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 -
The Cochrane Database of Systematic... Oct 2023Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled... (Review)
Review
BACKGROUND
Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019.
OBJECTIVES
To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital.
SEARCH METHODS
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 2 December 2022) with no restrictions. We searched two trial registries for ongoing trials (to 2 December 2022) and checked the reference lists of reviews and included articles for additional studies.
SELECTION CRITERIA
Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence certainty using GRADE.
MAIN RESULTS
In total, we included eight trials involving 906 infants and children aged up to three years. We included one new trial in this update. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. Five trials were conducted at single or multiple sites within a single high-income country (four in the USA, one in Qatar). Three trials included study sites in different countries. All three of these trials included study sites in one or more high-income countries (USA, Chile, New Zealand, Australia, Qatar), with two trials also including a study site in a middle-income country (Panama). Five of the eight trials were "supported" or "sponsored" by the trial drug manufacturers. The evidence is very uncertain about the effect of immunoglobulins on mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 4 studies, 309 participants). There were four deaths - two amongst 98 children receiving immunoglobulins, and two amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however the study group of the child was not known and the data were not included in the analysis (very low-certainty evidence). The use of immunoglobulins in infants and children admitted to hospital with RSV proven LRTI probably results in little to no difference in the length of hospitalisation (mean difference (MD) -0.13 days, 95% CI -0.37 to 0.12; 6 studies, 737 participants; moderate-certainty evidence). Immunoglobulins may result in little to no difference in the number of children who experience one or more adverse events of any severity or seriousness compared to placebo (RR 1.18, 95% CI 0.78 to 1.78; 5 studies, 340 participants; low-certainty evidence) or the number of children who experience one or more adverse events judged by study investigators to be serious in nature, compared to placebo (RR 1.08, 95% CI 0.65 to 1.79; 4 studies, 238 participants; low-certainty evidence). Certainty of evidence for secondary outcomes was low. This evidence suggests that use of immunoglobulins results in little to no difference in the need for, or duration of, mechanical ventilation and the need for, or duration of, supplemental oxygen. The use of immunoglobulins does not reduce the need for admission to the intensive care unit (ICU) and when children are admitted to the ICU results in little to no difference in the duration of ICU stay.
AUTHORS' CONCLUSIONS
We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.
Topics: Infant; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Hospitalization; Adrenal Cortex Hormones; Respiratory Tract Infections; Oxygen
PubMed: 37870128
DOI: 10.1002/14651858.CD009417.pub3 -
Frontiers in Immunology 2023Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion...
INTRODUCTION
Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection.
METHODS
Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through and serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV.
RESULTS
Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model.
CONCLUSION
Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.
Topics: Infant; Humans; Animals; Palivizumab; Antibodies, Viral; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Complement System Proteins; Sigmodontinae
PubMed: 37901217
DOI: 10.3389/fimmu.2023.1283120 -
Euro Surveillance : Bulletin Europeen... Dec 2023A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab...
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.
Topics: Infant; Humans; Antibodies, Monoclonal; Palivizumab; Respiratory Syncytial Virus Infections; Spain; Respiratory Syncytial Viruses; Antiviral Agents; Respiratory Syncytial Virus, Human
PubMed: 38062942
DOI: 10.2807/1560-7917.ES.2023.28.49.2300606 -
Nursing Children and Young People Sep 2023Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in children. Premature infants and infants with underlying health issues...
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in children. Premature infants and infants with underlying health issues are at increased risk of developing severe RSV infection. Prophylactic treatment with palivizumab reduces their risk of hospitalisation.
AIM
To measure nurses' knowledge of RSV and RSV prophylaxis and explore their perceived potential barriers to palivizumab administration to children in the acute hospital setting.
METHOD
A non-experimental, quantitative fixed study design was adopted. A 17-item online questionnaire was used to survey nurses caring for children under the age of 1 year in an acute children's teaching hospital.
RESULTS
Questionnaires were completed by 144 nurses, giving a response rate of 53%. Respondents demonstrated an adequate knowledge of RSV and its prophylaxis but also some knowledge deficits, notably about the eligibility criteria for palivizumab. The most cited perceived potential barriers to palivizumab administration were uncertainty about which infants are eligible for it, forgetting to check whether a patient is due to receive a dose, parental refusal for treatment because their child is ill, and not knowing the contraindications of palivizumab.
CONCLUSION
Front-line hospital staff have a crucial role in identifying infants eligible for prophylactic RSV treatment, in initiating prophylaxis in a timely manner, in avoiding missed or delayed palivizumab doses during infants' hospital stays, and in educating families about the importance of RSV prevention.
Topics: Infant; Child; Humans; Palivizumab; Respiratory Syncytial Viruses; Antiviral Agents; Clinical Competence; Nurses; Respiratory Syncytial Virus Infections; Hospitalization
PubMed: 36752164
DOI: 10.7748/ncyp.2023.e1458 -
Vaccine Aug 2023Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model...
Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.
Topics: Humans; Infant, Newborn; Infant; Infant, Premature; Incidence; Respiratory Syncytial Virus Infections; Western Australia; Seasons; Respiratory Syncytial Virus, Human; Hospitalization; Palivizumab; Antiviral Agents
PubMed: 37474407
DOI: 10.1016/j.vaccine.2023.07.014 -
Pediatrics Jan 2024The 2022 seasonal respiratory syncytial virus (RSV) epidemic in Sydney, Australia saw an unprecedented number of RSV detections. We aimed to characterize genomic and...
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.
Topics: Infant; Humans; Female; Respiratory Syncytial Viruses; Antiviral Agents; Respiratory Syncytial Virus Infections; Phylogeny; Palivizumab; Genomics
PubMed: 38225912
DOI: 10.1542/peds.2023-063667