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Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479 -
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 -
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 -
Infection and Drug Resistance 2023Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing... (Review)
Review
Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing the risk of severe disease, hospitalization, long-term sequelae, and death from this pathogen in susceptible populations. In this sense, therapies specifically directed against hRSV are mainly based on monoclonal and polyclonal antibodies such as intravenous IgG (IVIG)-RSV and the monoclonal antibody palivizumab. However, these therapies are associated with significant limitations, including the need for the recruitment of a high number of convalescent volunteers who donate blood to procure IVIG-RSV and the costs associated with the need for repeated administrations of palivizumab. These limitations render this product not cost-effective for populations other than high-risk patients. These problems have underscored that it is still necessary to identify new safe and effective therapies for human use. However, these new therapies must benefit from a comparatively cheap production cost and the opportunity to be available to the high-risk population and anyone who requires treatment. Here, we review the different antibodies used to prevent the pathology caused by hRSV infection, highlighting therapies currently approved for human use and their clinical value. Also, the new, most promising candidates based on preclinical studies and clinical trial results are revised.
PubMed: 37063935
DOI: 10.2147/IDR.S379660 -
Open Forum Infectious Diseases Mar 2018Respiratory syncytial virus (RSV) infection is the most common cause of lower respiratory tract infection and the leading cause of hospitalization among young children,... (Review)
Review
Respiratory syncytial virus (RSV) infection is the most common cause of lower respiratory tract infection and the leading cause of hospitalization among young children, incurring high annual costs among US children under the age of 5 years. Palivizumab has been found to be effective in reducing hospitalization and preventing serious lower respiratory tract infections in high-risk infants. This paper presents a systematic review of the cost-effectiveness studies of palivizumab and describes the main highlights of a round table discussion with clinical, payer, economic, research method, and other experts. The objectives of the discussion were to (1) review the current state of clinical, epidemiology, and economic data related to severe RSV disease; (2) review new cost-effectiveness estimates of RSV immunoprophylaxis in US preterm infants, including a review of the field's areas of agreement and disagreement; and (3) identify needs for further research.
PubMed: 29516023
DOI: 10.1093/ofid/ofy031 -
Fukushima Journal of Medical Science Dec 2017Respiratory Syncytial Virus (RSV) is one of the most important viral pathogen related to acute lower respiratory infection in young children. The virus surface envelope... (Review)
Review
Respiratory Syncytial Virus (RSV) is one of the most important viral pathogen related to acute lower respiratory infection in young children. The virus surface envelope contains the G, F, and SH proteins as spike proteins. The F protein is considered to be a major antigenic target for the neutralizing (NT) epitope as only the F protein is essential for cell infection among the three viral envelope proteins, and it is more highly conserved than the G protein. Recently, four antigenic targets related to NT activity have been reported;site I, site II, site IV, and site zero (0). Site II is the target for palivizumab used throughout the world to suppress severe RSV infection as passive immunity in high-risk children since 1998. Under the recent conditions in which indications for palivizumab administered subjects are being expanded, palivizumab-resistant mutations have been confirmed overseas in children with RSV infection, although they remain infrequent. Therefore, continuous genetic analysis of the palivizumab-binding region of the F protein is necessary. In addition, as vaccine development progresses, RSV infection control is expected to improve greatly over the next decade.
Topics: Antiviral Agents; Drug Resistance, Viral; Epitopes; Mutation; Neutralization Tests; Palivizumab; Respiratory Syncytial Viruses; Viral Fusion Proteins
PubMed: 28867684
DOI: 10.5387/fms.2017-09 -
Journal of Infection and Chemotherapy :... Feb 2022Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections in children aged <5 years and is associated with long-term... (Review)
Review
INTRODUCTION
Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections in children aged <5 years and is associated with long-term respiratory morbidities such as recurrent wheezing and asthma, decreased lung function, and allergic sensitization. The objective of this review was to evaluate the epidemiology and burden of RSV infection in the pediatric population in Japan.
METHODS
Studies indexed in PubMed and ICHUSHI databases during January 2010-December 2020 were manually reviewed. Data on proportion of RSV infections, seasonality, length of stay (LoS), mortality, medical expenses, and palivizumab use were extracted from the selected articles.
RESULTS
Ninety-three articles were included (PubMed, 64; ICHUSHI, 29). The proportion of patients/samples with an RSV infection was 5.5%-66.7%, and 6.0%-29.9% in the inpatient and outpatient departments, respectively. RSV infections generally occurred during autumn/winter; however, recently the peak has shifted to summer. The LoS was variable and depended on factors such as age, infection severity, wheezing, and RSV subgroups. Mortality rates varied from <1% to 19% depending on the infection severity. The average daily hospitalization and intensive care unit cost was JPY 34,548 while intensive care unit incurred an additional cost of JPY 541,293. Palivizumab was indicated for high-risk infants and 0%-3% of patients required hospitalization despite palivizumab use.
CONCLUSIONS
RSV imposes a significant burden on the Japanese healthcare system, suggesting a need to create awareness among caregivers of children, pregnant women and healthcare professionals to ensure early recognition of infection and adequate treatment or prophylaxis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Cost of Illness; Female; Hospitalization; Humans; Infant; Japan; Palivizumab; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34952776
DOI: 10.1016/j.jiac.2021.11.007 -
Molecules (Basel, Switzerland) Mar 2022Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year... (Review)
Review
Respiratory syncytial virus infection (RSVI) is an acute medical and social problem in many countries globally. Infection is most dangerous for infants under one year old and the elderly. Despite its epidemiological relevance, only two drugs are registered for clinical use against RSVI: ribavirin (approved in a limited number of countries due to side effects) and palivizumab (Synagis), which is intended only for the prevention, but not the treatment, of infection. Currently, various research groups are searching for new drugs against RSV, with three main areas of research: small molecules, polymeric drugs (proteins and peptides), and plant extracts. This review is devoted to currently developed protein and peptide anti-RSV drugs.
Topics: Aged; Antiviral Agents; Humans; Infant; Palivizumab; Peptides; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 35408661
DOI: 10.3390/molecules27072263 -
Infection and Drug Resistance 2023Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients.... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most common respiratory viruses. It not only affects young children but also the elderly and immunocompromised patients. After the emergence of SARS-CoV-2 and the corona virus disease 2019 (COVID-19) era, a dramatic reduction in RSV activity was found, which coincided with the implementation of public health and social measures (PHSMs). However, the correlation is more complicated than we initially thought. After PHSMs were gradually lifted, a seasonality shift and a delayed RSV outbreak with greater number of infected patients were found in numerous countries, such as Israel, Australia, South Africa, New Zealand, France, United States, and Japan. Several hypotheses and possible reasons explaining the interaction between SARS-CoV-2 and RSV were mentioned. Since RSV vaccinations are still under investigation, administration of palivizumab should be considered in high-risk patients. In the post-COVID-19 era, greater attention should be paid to a further resurgence of RSV. In this narrative review, we conducted a thorough review of the current knowledge on the epidemiology of RSV during the COVID-19 era, the out-of-season outbreak of RSV, and the data on co-infection with RSV and SARS-CoV-2.
PubMed: 36743336
DOI: 10.2147/IDR.S396434 -
Cureus Dec 2023This systematic review and meta-analysis aimed to summarize the current evidence regarding the efficacy and safety of palivizumab as a prophylaxis for respiratory... (Review)
Review
This systematic review and meta-analysis aimed to summarize the current evidence regarding the efficacy and safety of palivizumab as a prophylaxis for respiratory syncytial virus (RSV) disease. We searched MEDLINE via PubMed, Scopus, Cochrane, Web of Science, Embase, and Science Direct from inception till November 2023. Studies that assessed the efficacy and safety of palivizumab in infants aged between 28 days and three months of age were included. We analyzed the data using Review Manager 5.4 software, with results pooled across studies and expressed as risk ratios (RR) with 95% confidence intervals (CI). A total of 10 studies were included. The effect estimates favored palivizumab over placebo regarding the hospitalization for RSV infection (RR=0.51, 95% CI: 0.40 to 0.65; P<0.00001) and ICU admission (RR=0.49, 95% CI: 0.30 to 0.81; P=0.005). On the other hand, the effect estimate showed no significant difference between palivizumab and placebo regarding all-cause mortality (RR=0.69, 95% CI: 0.42 to 1.15; P=0.16), lower respiratory tract infection (RR=0.42, 95% CI: 0.11 to 1.69; P=0.22), and need for mechanical ventilation (RR=0.75, 95% CI: 0.34 to 1.67; P=0.48). Palivizumab can be considered a prophylaxis for RSV disease in young children as it is safe, well-tolerated, and effective in reducing RSV hospitalizations. However, further research through high-quality randomized controlled trials is required to determine its efficacy as a therapeutic agent for established RSV infections.
PubMed: 38292946
DOI: 10.7759/cureus.51375