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Vaccine Jun 2016Respiratory syncytial virus (RSV) is an important cause of viral lower respiratory tract illness in infants and children globally, but no vaccine is currently available... (Review)
Review
Respiratory syncytial virus (RSV) is an important cause of viral lower respiratory tract illness in infants and children globally, but no vaccine is currently available to protect these vulnerable populations. Live-attenuated vaccine approaches have been in development for decades, but achieving the appropriate balance between immunogenicity and safety has proven difficult. Immunoprophylaxis with the neutralizing monoclonal antibody palivizumab is limited to high-risk infants, but cost requirements for multiple dosing make its use impractical in low- and middle-income countries. A growing number of RSV vaccine candidates using a variety of technologies and targeting diverse populations has emerged in recent years. There are now 60 RSV vaccine candidates in development that target pediatric and elderly populations. While most are at a preclinical stage, 16 candidates are in clinical development. This review summarizes current RSV vaccine research and development, including an overview of the vaccine platforms being used, the development stage of individual vaccine candidates, and gaps to be addressed to facilitate use of these vaccines to meet global health needs.
Topics: Biomedical Research; Clinical Trials as Topic; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 27105562
DOI: 10.1016/j.vaccine.2016.03.109 -
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 -
Frontiers in Pharmacology 2020Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very...
OBJECTIVE
Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs.
DESIGN
Prospective animal study.
SETTING
Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children's Research Institute, Melbourne, Australia.
SUBJECTS
Four weaned Border-Leicester/Suffolk lambs at 5 months of age.
INTERVENTIONS
Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure.
MEASUREMENTS AND MAIN RESULTS
Both the HYDRA and AeroNeb Go produced palivizumab aerosols in the 1-5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54-5.41μm) and the AeroNeb Go (3.07 ± 1.56 μm, range = 0.86-10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79-94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung.
CONCLUSIONS
Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections.
PubMed: 32973520
DOI: 10.3389/fphar.2020.01291 -
Vaccine Nov 2022Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal...
INTRODUCTION
Respiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials. We evaluate the cost-effectiveness of Nirsevimab intervention programmes in England and Wales.
METHODS
We used a dynamic model for RSV transmission, calibrated to data from England and Wales. We considered a suite of potential Nirsevimab programmes, including administration to all neonates (year-round); only neonates born during the RSV season (seasonal); or neonates born during the RSV season plus infants less than six months old before the start of the RSV season (seasonal + catch-up).
RESULTS
If administered seasonally to all infants at birth, we found that Nirsevimab would have to be priced at £63 or less per dose for at least 50% certainty that it could cost-effectively replace the current Palivizumab programme, using an ICER threshold of £20,000/QALY. An extended seasonal programme which includes a pre-season catch-up becomes the optimal strategy at a purchasing price of £32/dose or less for at least 50% certainty. At a purchasing price per dose of £5-32, the annual implementation costs of a seasonal programme could be as high as £2 million before a switch to a year-round strategy would be optimal.
DISCUSSION
Nirsevimab has the potential to be cost-effective in England and Wales not only for use in high-risk infants.
Topics: Infant; Infant, Newborn; Humans; Respiratory Syncytial Virus Infections; Wales; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal; England
PubMed: 36328884
DOI: 10.1016/j.vaccine.2022.10.041 -
The Pediatric Infectious Disease Journal Nov 2018Palivizumab provides passive immunity for respiratory syncytial virus (RSV), but poor adherence compromises protection. A hospital initiative promoted administration of...
BACKGROUND
Palivizumab provides passive immunity for respiratory syncytial virus (RSV), but poor adherence compromises protection. A hospital initiative promoted administration of first palivizumab doses at an outpatient clinic immediately after discharge. The objectives of this study were to evaluate the impact of the initiative on location and timing of first palivizumab dose, patient adherence, reimbursement, acquisition cost and RSV-positive hospital readmissions.
METHODS
This retrospective cohort study included pediatric patients who received palivizumab from 2012 to 2016. Three groups were compared: "before initiative," "transition" and "after initiative." Patients who did not qualify for palivizumab or who were eligible for palivizumab in previous RSV seasons were excluded. Multivariable logistic and linear regressions adjusted for patients' characteristics were used in outcome analysis.
RESULTS
After adjusting for patients' characteristics, there was a 13.5-fold (95% confidence interval: 5.9-30.5, P < 0.0001) increase in odds that patients would receive outpatient administration of palivizumab and 2.7-fold (95% confidence interval: 1.3-5.7, P = 0.0103) increase in odds of receiving the second dose within 35 days after initiative implementation compared with before. Although there was no significant difference in reimbursement percentage after initiative implementation (32% ± 30% after initiative and 31% ± 22% before), calculated palivizumab acquisition costs were 20.8% lower. RSV readmissions were not significantly different.
CONCLUSIONS
Implementation of an initiative with defined workflow, multidisciplinary collaboration, and early case management efforts to obtain insurance authorization increased outpatient administration of first palivizumab doses. Patient adherence improved as demonstrated by more timely receipt of the second palivizumab dose. There was no difference in reimbursement; however, acquisition cost decreased which is valuable considering low reimbursement rates. RSV-positive readmissions did not change significantly.
Topics: Ambulatory Care Facilities; Antiviral Agents; Drug Administration Schedule; Female; Hospitals; Humans; Infant; Insurance, Health, Reimbursement; Male; Medication Adherence; Palivizumab; Patient Discharge; Regression Analysis; Respiratory Syncytial Virus Infections; Retrospective Studies
PubMed: 29570593
DOI: 10.1097/INF.0000000000001999 -
The Pediatric Infectious Disease Journal Jul 2016Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks... (Review)
Review
BACKGROUND
Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies.
METHODS
Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE).
RESULTS
We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE).
CONCLUSIONS
Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors.
Topics: Gestational Age; Hospitalization; Humans; Incidence; Infant, Premature; Infant, Premature, Diseases; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Seasons; Treatment Outcome
PubMed: 27093166
DOI: 10.1097/INF.0000000000001163 -
F1000Research 2019Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually... (Review)
Review
Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies.
Topics: Aged; Antibodies, Monoclonal; Child, Preschool; Female; Humans; Infant; Palivizumab; Pregnancy; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; Viral Vaccines
PubMed: 31105933
DOI: 10.12688/f1000research.18749.1 -
Viruses Sep 2021Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of...
Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.
Topics: Animals; Antibodies, Viral; Cell Line; Cell- and Tissue-Based Therapy; Epithelial Cells; Fetal Blood; Humans; Immunity, Innate; Inflammation; Macrophages; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Pluripotent Stem Cells; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34696391
DOI: 10.3390/v13101960 -
Newborn (Clarksville, Md.) 2023Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in young infants. It is an enveloped, single-stranded, nonsegmented,...
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in young infants. It is an enveloped, single-stranded, nonsegmented, negative-strand RNA virus, a member of the family Pneumoviridae. Globally, RSV is responsible for 2.3% of deaths among neonates 0-27 days of age. Respiratory syncytial virus infection is most common in children aged below 24 months. Neonates present with cough and fever. Respiratory syncytial virus-associated wheezing is seen in 20% infants during the first year of life of which 2-3% require hospitalization. Reverse transcriptase polymerase chain reaction (RT-PCR) gives fast results and has higher sensitivity compared with culture and rapid antigen tests and are not affected by passively administered antibody to RSV. Therapy for RSV infection of the LRT is mainly supportive, and preventive measures like good hygiene and isolation are the mainstay of management. Standard precautions, hand hygiene, breastfeeding and contact isolation should be followed for RSV-infected newborns. Recent AAP guidelines do not recommend pavilizumab prophylaxis for preterm infants born at 29-35 weeks without chronic lung disease, hemodynamically significant congenital heart disease and coexisting conditions. RSV can lead to long-term sequelae such as wheezing and asthma, associated with increased healthcare costs and reduced quality of life.
PubMed: 38348152
DOI: 10.5005/jp-journals-11002-0073 -
Frontiers in Pediatrics 2021To define the impact of associated abnormalities on the efficacy of the novel subtropical guidelines for palivizumab prophylaxis on respiratory syncytial virus...
To define the impact of associated abnormalities on the efficacy of the novel subtropical guidelines for palivizumab prophylaxis on respiratory syncytial virus (RSV)-related hospitalizations in patients with hemodynamically significant congenital heart disease (hsCHD). This prospective study enrolled every patient seen at a tertiary care center for hsCHD, who was born between 2014 and 2018 and received at least 1 dose of palivizumab, according to the subtropical guidelines. The patients were followed until the age of 2 years. A total of 772 patients (49% male) were enrolled. Cyanotic CHD was seen in 46% of patients, of whom 23% had associated abnormalities. Lung/airway abnormalities (14%) were the most common followed by the genetic syndromes associated with CHD (7.3%). Among the 772 patients, RSV-related hospitalizations occurred in 3.2 and 2.2% children aged ≤ 12 and 13-24 months, respectively. Most of the RSV infections occurred in patients no longer satisfying the criteria for palivizumab prophylaxis. The patients with associated abnormalities but not the type of CHD, patient age, and patient sex were risk factors for RSV-related hospitalizations. The rates of RSV-related hospitalizations, admission to the intensive care unit, and endotracheal intubation were higher for patients with associated anomalies than for other patients before 24 months of age (10.2 vs. 4.0%, 67 vs. 33%, and 39 vs. 4.2%, = 0.004, 0.06, 0.013, respectively). Children with abnormalities, especially genetic syndromes and lung/airway problems associated with CHD, are at high risk for RSV-related hospitalization. Our current subtropical guidelines for palivizumab prophylaxis in patients with hsCHD, should be revised to include the results of this study.
PubMed: 35071127
DOI: 10.3389/fped.2021.756787