-
Paediatric Drugs Nov 2023Pfizer is developing a bivalent respiratory syncytial virus (RSV) prefusion F subunit vaccine (RSVpreF; ABRYSVO™) for preventing RSV illness in infants and individuals... (Review)
Review
Pfizer is developing a bivalent respiratory syncytial virus (RSV) prefusion F subunit vaccine (RSVpreF; ABRYSVO™) for preventing RSV illness in infants and individuals aged ≥ 60 years. RSVpreF received approval for vaccination of pregnant individuals to help protect infants against RSV illness on 21 August 2023 in the USA. RSVpreF is also approved in the USA (31 May 2023) for active immunization of individuals aged ≥ 60 years for the prevention of lower respiratory tract disease (LRTD) caused by RSV. In the EU, RSVpreF has received approval for both indications, and it has been submitted for regulatory approval in Canada (both indications) and in Japan (maternal immunization to protect infants). This article summarizes the milestones in the development of RSVpreF leading to the approval for use in pregnant individuals to prevent LRTD in infants.
Topics: Female; Pregnancy; Humans; Infant; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Viral Fusion Proteins; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Vaccines, Subunit
PubMed: 37831328
DOI: 10.1007/s40272-023-00598-3 -
Clinical Microbiology and Infection :... Dec 2023Respiratory syncytial virus (RSV) is widely known as a frequent cause of respiratory distress among adults, particularly in older people. Recent years have witnessed... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is widely known as a frequent cause of respiratory distress among adults, particularly in older people. Recent years have witnessed several improvements in respiratory virus detection, leading to more questions about therapeutic management strategies.
OBJECTIVES
This narrative review focuses on the RSV burden in older people and adults with risk factors and provides an update on the main recent developments regarding managing this infection.
SOURCES
A comprehensive PubMed search was conducted till August 2023 to identify studies on RSV among the adult population. We included observational studies, RCTs on vaccines, and different therapies.
CONTENT
This review should give clinicians an overview of RSV epidemiology and burden among older people and adults with pre-existing risk factors, the most recent randomized clinical trials on RSV vaccines, and the existing data on the different therapeutics existing and under development.
IMPLICATIONS
There is a growing body of evidence on RSV burden in adults. The landscape of preventive and curative treatments is quickly evolving.
Topics: Adult; Humans; Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines; Risk Factors
PubMed: 37666450
DOI: 10.1016/j.cmi.2023.08.028 -
BMC Infectious Diseases Oct 2023Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections resulting in a significant burden worldwide, particularly in children and older...
Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections resulting in a significant burden worldwide, particularly in children and older adults. This collection calls for original research papers that advance our understanding of the epidemiology, evolution, diagnosis, clinical management, and prevention of RSV infections.
Topics: Child; Humans; Infant; Aged; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Risk Factors; Hospitalization
PubMed: 37891488
DOI: 10.1186/s12879-023-08730-x -
Ugeskrift For Laeger Mar 2024Respiratory syncytial virus (RSV is) a common respiratory virus responsible for considerable morbidity and mortality among infants, elderly with comorbidity, and...
Respiratory syncytial virus (RSV is) a common respiratory virus responsible for considerable morbidity and mortality among infants, elderly with comorbidity, and immunocompromised adults. Two vaccines, Abrysvo and Arexvy, have been approved for prevention of severe RSV infection in adults ≥ 60 years of age. In addition, Abrysvo is approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection. Currently, there is no national recommendation for the use of the vaccines, but vaccination of elderly at highest risk of severe RSV infection should be considered in a shared clinical decision making.
Topics: Infant; Adult; Pregnancy; Female; Humans; Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 38533866
DOI: 10.61409/V12230800 -
Science Translational Medicine Aug 2023The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization...
The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01-elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.
Topics: Humans; Aged; Respiratory Syncytial Viruses; Respiratory Syncytial Virus Infections; Vaccines; Antigens, Viral
PubMed: 37611082
DOI: 10.1126/scitranslmed.adg6050 -
Nature Communications Jul 2023Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313)... (Randomized Controlled Trial)
Randomized Controlled Trial
Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
Topics: Humans; Infant; Antibodies, Monoclonal, Humanized; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 37468530
DOI: 10.1038/s41467-023-40057-8 -
World Journal of Pediatrics : WJP Jan 2024Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections and is responsible for about 3 million hospitalizations and more than 100,000 deaths annually in children younger than 5 years, representing a major global healthcare burden. There is a great unmet need for new agents and universal strategies to prevent RSV infections in early life. A multidisciplinary consensus development group comprising experts in epidemiology, infectious diseases, respiratory medicine, and methodology aims to develop the current consensus to address clinical issues of RSV infections in children.
DATA SOURCES
The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, using variations in terms for "respiratory syncytial virus", "RSV", "lower respiratory tract infection", "bronchiolitis", "acute", "viral pneumonia", "neonatal", "infant" "children", and "pediatric".
RESULTS
Evidence-based recommendations regarding diagnosis, treatment, and prevention were proposed with a high degree of consensus. Although supportive care remains the cornerstone for the management of RSV infections, new monoclonal antibodies, vaccines, drug therapies, and viral surveillance techniques are being rolled out.
CONCLUSIONS
This consensus, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of RSV infections. Further improvements in the management of RSV infections will require generating the highest quality of evidence through rigorously designed studies that possess little bias and sufficient capacity to identify clinically meaningful end points.
Topics: Child; Humans; Respiratory Syncytial Virus Infections; Consensus; Respiratory Syncytial Viruses; Bronchiolitis; Respiratory Tract Infections; Hospitalization
PubMed: 38064012
DOI: 10.1007/s12519-023-00777-9 -
Cell Host & Microbe Aug 2023Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections pose a significant health burden. Using pre-fusion conformation fusion (F) proteins, we isolated a panel of anti-F antibodies from a human donor. One antibody (RSV-199) potently cross-neutralized 8 RSV and hMPV strains by recognizing antigenic site III, which is partially conserved in RSV and hMPV F. Next, we determined the cryoelectron microscopy (cryo-EM) structures of RSV-199 bound to RSV F trimers, hMPV F monomers, and an unexpected dimeric form of hMPV F. These structures revealed how RSV-199 engages both RSV and hMPV F proteins through conserved interactions of the antibody heavy-chain variable region and how variability within heavy-chain complementarity-determining region 3 (HCDR3) can be accommodated at the F protein interface in site-III-directed antibodies. Furthermore, RSV-199 offered enhanced protection against RSV A and B strains and hMPV in cotton rats. These findings highlight the mechanisms of broad neutralization and therapeutic potential of RSV-199.
Topics: Humans; Metapneumovirus; Antibodies, Neutralizing; Antibodies, Viral; Cryoelectron Microscopy; Respiratory Syncytial Virus, Human; Immunoglobulin Variable Region; Viral Fusion Proteins
PubMed: 37516111
DOI: 10.1016/j.chom.2023.07.002 -
The Journal of Infectious Diseases Aug 2023In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women.
METHODS
In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively.
RESULTS
RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth.
CONCLUSIONS
RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns.
CLINICAL TRIALS REGISTRATION
NCT04126213.
Topics: Pregnancy; Humans; Female; Infant; Infant, Newborn; Adolescent; Young Adult; Adult; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Antibodies, Neutralizing; Mothers; Respiratory Syncytial Virus Infections; Viral Fusion Proteins; Placenta; Immunogenicity, Vaccine; Respiratory Syncytial Virus, Human
PubMed: 36722147
DOI: 10.1093/infdis/jiad024 -
The Lancet. Infectious Diseases Jul 2023Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire... (Observational Study)
Observational Study
Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data.
BACKGROUND
Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021.
METHODS
We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank.
FINDINGS
We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40·0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1·0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins.
INTERPRETATION
The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time.
FUNDING
AstraZeneca and Sanofi.
Topics: Infant; Humans; Respiratory Syncytial Virus Infections; Prospective Studies; Pilot Projects; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human; Glycoproteins; Binding Sites
PubMed: 36940703
DOI: 10.1016/S1473-3099(23)00062-2