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1.
Hum Vaccin Immunother ; 20(1): 2327142, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38508690

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Lactente , Animais , Humanos , Recém-Nascido , Idoso , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais , Anticorpos Neutralizantes , Proteínas Virais de Fusão/genética , Mamíferos/metabolismo
2.
Ital J Pediatr ; 50(1): 56, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528568

RESUMO

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.


Assuntos
Displasia Broncopulmonar , Cardiopatias Congênitas , Infecções por Vírus Respiratório Sincicial , Lactente , Recém-Nascido , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Recém-Nascido Prematuro , Estudos Retrospectivos , Estudos de Coortes , Palivizumab/uso terapêutico , Hospitalização , Cardiopatias Congênitas/epidemiologia , Displasia Broncopulmonar/epidemiologia , Antivirais/uso terapêutico
3.
Molecules ; 29(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338343

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Lactente , Idoso , Antivirais/farmacologia , Antivirais/uso terapêutico , Palivizumab/farmacologia , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Antirretrovirais/uso terapêutico
4.
J Pediatric Infect Dis Soc ; 13(2): 136-143, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279954

RESUMO

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.


Assuntos
Síndromes de Imunodeficiência , Infecções por Vírus Respiratório Sincicial , Criança , Humanos , Lactente , Palivizumab/uso terapêutico , Vírus Sinciciais Respiratórios , Antivirais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Hospitalização
5.
Pediatrics ; 153(2)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38225912

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sinciciais Respiratórios , Lactente , Humanos , Feminino , Antivirais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Filogenia , Palivizumab , Genômica
6.
Am J Obstet Gynecol ; 230(2): B41-B49, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37914061

RESUMO

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.


Assuntos
Perinatologia , Infecções por Vírus Respiratório Sincicial , Lactente , Criança , Gravidez , Feminino , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Palivizumab/uso terapêutico , Vírus Sinciciais Respiratórios , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico
7.
Paediatr Drugs ; 26(2): 101-112, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38032456

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas , Gravidez , Estados Unidos , Criança , Lactente , Feminino , Humanos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Palivizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , União Europeia
8.
Nurs Womens Health ; 28(1): 75-79, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070539

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados , Infecções por Vírus Respiratório Sincicial , Infecções Respiratórias , Lactente , Criança , Humanos , Estados Unidos , Palivizumab/uso terapêutico , Vírus Sinciciais Respiratórios , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Hospitalização , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/induzido quimicamente , Imunização
9.
Pediatr Pulmonol ; 59(3): 743-749, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38116923

RESUMO

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.


Assuntos
Asma , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Recém-Nascido , Humanos , Palivizumab/uso terapêutico , Recém-Nascido Prematuro , Seguimentos , Antivirais/uso terapêutico , Estudos Prospectivos , Estudos de Casos e Controles , Sons Respiratórios/diagnóstico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Asma/epidemiologia , Asma/prevenção & controle , Asma/tratamento farmacológico , Hospitalização
10.
Antiviral Res ; 222: 105783, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38145755

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Criança , Humanos , Idoso , Antivirais/uso terapêutico , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Anticorpos Monoclonais/uso terapêutico
11.
Euro Surveill ; 28(49)2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38062942

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Humanos , Anticorpos Monoclonais/uso terapêutico , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Espanha , Vírus Sinciciais Respiratórios , Antivirais/uso terapêutico
14.
Viruses ; 15(11)2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38005952

RESUMO

(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the "proof-of-principle" effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Animais , Ovinos , Palivizumab , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Antivirais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico
15.
Front Immunol ; 14: 1283120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901217

RESUMO

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 in vitro and ex vivo 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 in vitro ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ex vivo 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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Humanos , Animais , Palivizumab/uso terapêutico , Anticorpos Antivirais , Proteínas do Sistema Complemento/uso terapêutico , Sigmodontinae
16.
Hum Vaccin Immunother ; 19(2): 2252289, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37828711

RESUMO

Palivizumab has been shown to decrease RSV-related hospitalization (RSVH) risk and reduce RSVH severity. American Academy of Pediatrics (AAP) guidance on administration of palivizumab has changed over time; in 2014, palivizumab was no longer recommended in preterm infants born at 29 weeks gestational age (wGA) or later. This study's objective was to describe RSVH risk and severity in preterm infants (29-34 wGA) without comorbidities relative to healthy term infants and to each other by gestational age. Using the MarketScan Multi-State Medicaid and Commercial Databases, infants born from July 1, 2014 to June 30, 2019, at 29-34 wGA (preterm) and >37 wGA (term) were identified. During RSV seasons (November to March) from 2014 to 2020, claims incurred by infants while they were <6 months old were evaluated for RSVH and RSVH characteristics. This study included 63,351 preterm infants and 1,076,389 term infants without outpatient palivizumab administration. Rate of RSVH was higher in infants with lower wGA at birth and ranged 3.32-5.72 per 100 infant-seasons in Medicaid-insured infants and 3.21-4.84 in commercially insured infants. Relative risk of RSVH was 5-8 times higher in Medicaid-insured preterm infants and 3-5 times higher in commercially insured preterm infants compared to term infants. ICU admissions and mechanical ventilation were more common during RSVH in preterm infants relative to term infants. RSV-related outpatient healthcare utilization was also 2-3 times higher in preterm infants born at 31-34 wGA. Increased utilization of palivizumab among infants born at 29-34 wGA may decrease RSVH rates and result in less severe course in preterm infants with RSVH.


Assuntos
Recém-Nascido Prematuro , Infecções por Vírus Respiratório Sincicial , Lactente , Recém-Nascido , Humanos , Criança , Estados Unidos , Palivizumab/uso terapêutico , Idade Gestacional , Antivirais/uso terapêutico , Pacientes Ambulatoriais , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Hospitalização
17.
Front Public Health ; 11: 1261165, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829087

RESUMO

Introduction: Detection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness. Methods: We compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR. Results: RSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman's ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities. Discussion: Quantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Criança , Palivizumab/uso terapêutico , Antivirais/uso terapêutico , Ontário/epidemiologia , Vigilância Epidemiológica Baseada em Águas Residuárias , Estações do Ano , Cidades , Águas Residuárias , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
18.
Pediatrics ; 152(5)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37682622
19.
J Biol Chem ; 299(11): 105270, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37734558

RESUMO

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 (AIPVHH) as synthetic receptors. Importantly, Palivizumab is neither cross-reactive with human proteins nor immunogenic. For the synthetic receptors, AIPVHH were fused to the activating interleukin-6 cytokine receptor gp130 and the apoptosis-inducing receptor Fas. We found that the synthetic cytokine receptor AIPVHHgp130 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.


Assuntos
Receptores Artificiais , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Palivizumab/farmacologia , Palivizumab/uso terapêutico , Receptores Artificiais/metabolismo , Receptores Artificiais/uso terapêutico , Receptores de Citocinas , Citocinas , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Ligantes , Antivirais/farmacologia , Antivirais/uso terapêutico
20.
PLoS One ; 18(8): e0289828, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561741

RESUMO

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.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Recém-Nascido , Lactente , Humanos , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Análise Custo-Benefício , Idade Gestacional , Antivirais/uso terapêutico , Recém-Nascido Prematuro , Anticorpos Monoclonais Humanizados/uso terapêutico , Fatores de Risco , Hospitalização , Itália/epidemiologia
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