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Antiviral Research Feb 2024The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with... (Review)
Review
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.
Topics: Infant; Child; Humans; Aged; Respiratory Syncytial Virus, Human; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal
PubMed: 38145755
DOI: 10.1016/j.antiviral.2023.105783 -
Pharmacotherapy Jun 2017Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care for infants with CF remains controversial.
OBJECTIVE
To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years.
METHODS
Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis.
RESULTS
The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880).
CONCLUSIONS
Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF.
Topics: Antiviral Agents; Child; Cohort Studies; Cross-Sectional Studies; Cystic Fibrosis; Humans; Infant; Palivizumab; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 28423192
DOI: 10.1002/phar.1936 -
Turk Pediatri Arsivi Jun 2018Respiratory syncytial virus is one of the major causes of respiratory tract infections during infancy with high rates of hospitalization and mortality during the first... (Review)
Review
Respiratory syncytial virus is one of the major causes of respiratory tract infections during infancy with high rates of hospitalization and mortality during the first years of life. It is the most common cause of acute bronchiolitis and viral pneumonia in children below two years of age and second the most common cause of postneonatal infant mortality all around the world following malaria. In addition, the virus has been causally linked to recurrent wheezing and associated with pediatric asthma. The respiratory syncytial virus infections tend to be severe in high risk patients such as patients below six months of age, with prematurity, congenital heart diseases, neuromuscular diseases and immune deficiencies. No specific treatment is available for respiratory syncytial virus infections to date. Severe cases require supportive therapy, mainly oxygen supplementation and hydration, and less frequently, ventilatory support. Because there is no vaccine to prevent respiratory syncytial virus infections or clinically effective treatment to administer to children with respiratory syncytial virus infection, immunoprophylaxis with palivizumab is currently the only method for reducing morbidity associated with severe respiratory syncytial virus in high-risk infants.
PubMed: 30116126
DOI: 10.5152/TurkPediatriArs.2018.6939 -
The Lancet. Respiratory Medicine Mar 2017
Review
Topics: Antiviral Agents; Humans; Infant; Infant, Newborn; Infant, Premature; Palivizumab; Preventive Medicine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 28219614
DOI: 10.1016/S2213-2600(17)30050-4 -
Viruses Apr 2023The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to...
The respiratory syncytial virus (RSV) causes significant respiratory disease in young infants and the elderly. Immune prophylaxis in infants is currently limited to palivizumab, an anti-RSV fusion (F) protein monoclonal antibody (mAb). While anti-F protein mAbs neutralize RSV, they are unable to prevent aberrant pathogenic responses provoked by the RSV attachment (G) protein. Recently, the co-crystal structures of two high-affinity anti-G protein mAbs that bind the central conserved domain (CCD) at distinct non-overlapping epitopes were solved. mAbs 3D3 and 2D10 are broadly neutralizing and block G protein CX3C-mediated chemotaxis by binding antigenic sites γ1 and γ2, respectively, which is known to reduce RSV disease. Previous studies have established 3D3 as a potential immunoprophylactic and therapeutic; however, there has been no similar evaluation of 2D10 available. Here, we sought to determine the differences in neutralization and immunity to RSV Line19F infection which recapitulates human RSV infection in mouse models making it useful for therapeutic antibody studies. Prophylactic (24 h prior to infection) or therapeutic (72 h post-infection) treatment of mice with 3D3, 2D10, or palivizumab were compared to isotype control antibody treatment. The results show that 2D10 can neutralize RSV Line19F both prophylactically and therapeutically, and can reduce disease-causing immune responses in a prophylactic but not therapeutic context. In contrast, 3D3 was able to significantly ( < 0.05) reduce lung virus titers and IL-13 in a prophylactic and therapeutic regimen suggesting subtle but important differences in immune responses to RSV infection with mAbs that bind distinct epitopes.
Topics: Mice; Humans; Animals; Aged; Palivizumab; Antibodies, Viral; Viral Fusion Proteins; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Epitopes
PubMed: 37243153
DOI: 10.3390/v15051067 -
Journal of Paediatrics and Child Health Dec 2020Respiratory syncytial virus (RSV) continues to be a significant source of morbidity and mortality in both adults and children. Natural infection confers incomplete...
Respiratory syncytial virus (RSV) continues to be a significant source of morbidity and mortality in both adults and children. Natural infection confers incomplete protection, permitting recurrent episodes. Treatment remains limited to supportive care. Initial endeavours to develop a vaccine resulted in an unexpected enhancement of RSV disease and increased recipient mortality. Current proposed strategies to prevent RSV infection rely on the principles of active and passive immunisation and utilise the highly conserved RSV F-protein. Maternal vaccines administered in pregnancy may provide protection; trials are ongoing. Palivizumab, a monoclonal antibody, has a moderate preventative efficacy. A similar newer longer lasting formulation appears promising. A number of other novel options are being developed and are undergoing assessment. Progress has been made, with more vaccine candidates under consideration. We are edging closer to an effective solution to prevent RSV infection. If successful, the impact on paediatric morbidity, mortality, workload and cost will be substantial.
Topics: Adult; Antiviral Agents; Child; Female; Humans; Immunization; Palivizumab; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 33089944
DOI: 10.1111/jpc.15232 -
Jornal de Pediatria 2023Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use.... (Review)
Review
OBJECTIVES
Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy.
DATA SOURCE
A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022.
DATA SYNTHESIS
Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population.
CONCLUSIONS
The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.
Topics: Infant; Pregnancy; Female; Child; Humans; Respiratory Syncytial Virus Vaccines; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Immunization, Passive; Antibodies, Monoclonal
PubMed: 36402228
DOI: 10.1016/j.jped.2022.10.004 -
International Journal of Molecular... Apr 2021Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in... (Review)
Review
Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.
Topics: Antiviral Agents; Humans; Infant; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 33918185
DOI: 10.3390/ijms22073703 -
American Journal of Perinatology Sep 2020Infections caused by respiratory viruses in neonates during their stay in the neonatal intensive care unit (NICU) are more frequent than generally suspected. Respiratory... (Review)
Review
Infections caused by respiratory viruses in neonates during their stay in the neonatal intensive care unit (NICU) are more frequent than generally suspected. Respiratory syncytial virus (RSV), a highly contagious pathogen, is the most common etiologic agent, and it carries a high risk of nosocomial spread. During the RSV season, overcrowding of the NICU, shortage of staff, and unrestricted visitors are factors predisposing outbreaks. Since signs and symptoms of RSV infections are no specific, a high index of suspicion is essential to prevent or limit epidemics. The etiologic agent should be confirmed and polymerase chain reaction (PCR) is the gold-standard test. Shedding of the virus by infected preterm infants is prolonged and RSV lasts for several hours on countertops and other surfaces. The first case should be isolated and strict cohorting must be instituted. Compliance with hand washing must be warranted. Wearing gowns and gloves may help. The severity of nosocomial RSV infections tends to be higher than that of those community acquired. There is no uniform recommendation to start palivizumab during hospital stay of premature and high-risk infants. The use of this monoclonal antibody to stop or limit the spread of outbreaks is controversial. It is recommended by some professional organizations and not by others but its use during large outbreaks in infants at risk who share the room with infected neonates is not uncommon. KEY POINTS: · During peak community epidemic, NICU outbreaks of RSV infections are not uncommon.. · High index of suspicion is essential as initial signs are nonspecific in preterm neonates.. · Isolation and cohorting, strict hand washing, gowns, gloves, and eventually palivizumab are main tools for management..
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Cross Infection; Disease Outbreaks; Humans; Infant, Newborn; Infection Control; Intensive Care Units, Neonatal; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 32898879
DOI: 10.1055/s-0040-1714081 -
The Cochrane Database of Systematic... Jul 2016Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antiviral Agents; Cystic Fibrosis; Drug Administration Schedule; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 27439110
DOI: 10.1002/14651858.CD007743.pub6