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RSV Specific Antibodies in Pregnant Women and Subsequent Risk of RSV Hospitalization in Young Infants.

J Infect Dis 2021 Jun 15. Epub 2021 Jun 15.

Helsinki University Hospital and University of Helsinki, Children's Hospital, Helsinki, Finland.

Background: The fusion (F) glycoprotein of respiratory syncytial virus (RSV) represents the major neutralizing antigen, and antibodies against the pre-F conformation have the most potent neutralizing activity. This study aimed to assess the correlation between maternal antibody (Ab) titers against the pre-F, post-F and G glycoproteins and the child's risk of developing severe RSV bronchiolitis early in infancy.

Methods: We identified previously healthy term infants less than 3 months of age hospitalized with RSV bronchiolitis from December 2015 to March 2016. Read More

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Level of maternal respiratory syncytial virus (RSV) F antibodies in hospitalized children and correlates of protection.

Int J Infect Dis 2021 Aug 10;109:56-62. Epub 2021 Jun 10.

Biomedical Research Center, Qatar University, Qatar; College of Health Sciences, Qatar University, Qatar. Electronic address:

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory infection among children and no vaccine is available. The stabilized form of the fusion (F) protein - pre-F - is a leading vaccine candidate to target different populations, including pregnant women. This study aimed to determine the magnitude and nature of RSV-directed maternal antibodies (matAbs) in hospitalized children with RSV infection. Read More

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In silico virtual screening of lead compounds for major antigenic sites in respiratory syncytial virus fusion protein.

Emergent Mater 2021 May 3:1-11. Epub 2021 May 3.

Biomedical Research Center, Qatar University, Doha, 2713 Qatar.

Human respiratory syncytial virus (RSV) is a leading ubiquitous respiratory pathogen in newborn infants, young children, and the elderly, with no vaccine available to date. The viral fusion glycoprotein (RSV F) plays an essential role in the infection process, and it is a primary target of neutralizing antibodies, making it an attractive site for vaccine development. With this in view, there is a persistent need to identify selective antiviral drugs against RSV, targeting the major antigenic sites on the F protein. Read More

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Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial.

Lancet Respir Med 2021 Apr 14. Epub 2021 Apr 14.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: Multiple active vaccination approaches have proven ineffective in reducing the substantial morbidity and mortality caused by respiratory syncytial virus (RSV) in infants and older adults (aged ≥65 years). A vaccine conferring a substantial and sustainable boost in neutralising activity is required to protect against severe RSV disease. To that end, we evaluated the safety and immunogenicity of DS-Cav1, a prefusion F subunit vaccine. Read More

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Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.

Immunity 2021 04 5;54(4):769-780.e6. Epub 2021 Apr 5.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. Read More

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Prevention of Respiratory Syncytial Virus Infection in Healthy Adults by a Single Immunization of Ad26.RSV.preF in a Human Challenge Study.

J Infect Dis 2021 Jan 5. Epub 2021 Jan 5.

Janssen Vaccines & Prevention BV, Leiden, The Netherlands.

Background: Respiratory syncytial virus (RSV) is a significant cause of severe lower respiratory tract disease in children and older adults, but has no approved vaccine. This study assessed the potential of Ad26.RSV. Read More

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January 2021

The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination.

Vaccine 2020 11 29;38(50):7916-7927. Epub 2020 Oct 29.

GSK, Via Fiorentina 1, 53100 Siena, Italy. Electronic address:

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. Read More

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November 2020

A Parainfluenza Virus Vector Expressing the Respiratory Syncytial Virus (RSV) Prefusion F Protein Is More Effective than RSV for Boosting a Primary Immunization with RSV.

J Virol 2020 12 22;95(2). Epub 2020 Dec 22.

RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

Live-attenuated pediatric vaccines for intranasal administration are being developed for human respiratory syncytial virus (RSV), an important worldwide pediatric respiratory pathogen that lacks a licensed vaccine or suitable antiviral drug. We evaluated a prime-boost strategy in which primary immunization with RSV was boosted by secondary immunization with RSV or with a chimeric recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3) vector expressing the RSV fusion F protein. The vector-expressed F protein had been engineered (DS-Cav1 mutations) for increased stability in the highly immunogenic prefusion (pre-F) conformation, with or without replacement of its transmembrane and cytoplasmic tail domains with their counterparts from bovine parainfluenza virus type 3 (BPIV3) F protein to direct incorporation into the vector virion for increased immunogenicity. Read More

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December 2020

Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults.

J Infect Dis 2021 Feb;223(4):699-708

Janssen Vaccines & Prevention, Leiden, the Netherlands.

Background: Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26. Read More

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February 2021

Bovine IgG Prevents Experimental Infection With RSV and Facilitates Human T Cell Responses to RSV.

Front Immunol 2020 6;11:1701. Epub 2020 Aug 6.

Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.

Respiratory syncytial virus (RSV) infections represent a major burden of disease in infants and are the second most prevalent cause of death worldwide. Human milk immunoglobulins provide protection against RSV. However, many infants depend on processed bovine milk-based nutrition, which lacks intact immunoglobulins. Read More

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Structure-Based Design of Nipah Virus Vaccines: A Generalizable Approach to Paramyxovirus Immunogen Development.

Front Immunol 2020 11;11:842. Epub 2020 Jun 11.

Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

Licensed vaccines or therapeutics are rarely available for pathogens with epidemic or pandemic potential. Developing interventions for specific pathogens and defining generalizable approaches for related pathogens is a global priority and inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses a significant epidemic threat, and zoonotic transmission from bats-to-humans with high fatality rates occurs almost annually. Read More

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A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain.

Sci Immunol 2020 05;5(47)

Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.

A stabilized form of the respiratory syncytial virus (RSV) fusion (F) protein has been explored as a vaccine to prevent viral infection because it presents several potent neutralizing epitopes. Here, we used a structure-based rational design to optimize antigen presentation and focus antibody (Ab) responses to key epitopes on the pre-fusion (pre-F) protein. This protein was fused to ferritin nanoparticles (pre-F-NP) and modified with glycans to mask nonneutralizing or poorly neutralizing epitopes to further focus the Ab response. Read More

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Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years.

J Infect Dis 2020 08;222(6):979-988

Janssen Vaccines & Prevention, Leiden, the Netherlands.

Background: Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV. Read More

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Comparisons of Antibody Populations in Different Pre-Fusion F VLP-Immunized Cotton Rat Dams and Their Offspring.

Vaccines (Basel) 2020 Mar 18;8(1). Epub 2020 Mar 18.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Respiratory syncytial virus (RSV) infection poses a significant risk for infants. Since the direct vaccination of infants is problematic, maternal vaccination may provide a safer, more effective approach to their protection. In the cotton rat (CR) model, we have compared the immunization of pregnant CR dams with virus-like particles assembled with the prototype mutation stabilized pre-fusion F protein, DS-Cav1, as well two alternative mutation stabilized pre-fusion proteins (UC-2 F, UC-3 F) and showed that the alternative pre-fusion F VLPs protected the offspring of immunized dams significantly better than DS-Cav1 F VLPs (Blanco, et al. Read More

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Human respiratory syncytial virus F protein expressed in Pichia pastoris or Escherichia coli induces protective immunity without inducing enhanced respiratory disease in mice.

Arch Virol 2020 May 6;165(5):1057-1067. Epub 2020 Mar 6.

NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.

Human respiratory syncytial virus (hRSV) is the primary cause of severe respiratory tract disease in children and infants as well as in elderly and immunocompromised adults. The fusion protein (F) of hRSV is the major antigen eliciting a neutralizing antibody response and protective immunity in the host, especially those recognizing the prefusion F protein (pre-F). In this study, we made genetic constructs for expression of a recombinant prefusion F protein in Pichia pastoris GS115, called RGF. Read More

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Human parainfluenza virus type 3 expressing the respiratory syncytial virus pre-fusion F protein modified for virion packaging yields protective intranasal vaccine candidates.

PLoS One 2020 11;15(2):e0228572. Epub 2020 Feb 11.

RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

Human respiratory syncytial virus (RSV) and parainfluenza virus type 3 (HPIV3) are among the most common viral causes of childhood bronchiolitis and pneumonia worldwide, and lack effective antiviral drugs or vaccines. Recombinant (r) HPIV3 was modified to express the RSV fusion (F) glycoprotein, the major RSV neutralization and protective antigen, providing a live intranasal bivalent HPIV3/RSV vaccine candidate. This extends previous studies using a chimeric bovine-human PIV3 vector (rB/HPIV3). Read More

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Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice: A Proof of Concept Study.

Pharmaceutics 2019 Oct 3;11(10). Epub 2019 Oct 3.

Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Currently, there is an increasing interest to apply pre-fusion (pre-F) protein of respiratory syncytial virus (RSV) as antigen for the development of a subunit vaccine. A pre-F-containing powder would increase the flexibility regarding the route of administration. For instance, a pre-F-containing powder could be incorporated into a single-injection system releasing a primer, and after a lag time, a booster. Read More

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October 2019

Alternative Virus-Like Particle-Associated Prefusion F Proteins as Maternal Vaccines for Respiratory Syncytial Virus.

J Virol 2019 12 13;93(23). Epub 2019 Nov 13.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Maternal vaccination may be the most effective and safest approach to the protection of infants from respiratory syncytial virus (RSV) infection, a severe acute lower respiratory tract disease in infants and young children worldwide. We previously compared five different virus-like particle (VLP)-associated, mutation-stabilized prefusion F (pre-F) proteins, including the prototype DS-Cav1 F VLPs. We showed that alternative versions of prefusion F proteins have different conformations and induce different populations of anti-F protein antibodies. Read More

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December 2019

The Optimal Concentration of Formaldehyde is Key to Stabilizing the Pre-Fusion Conformation of Respiratory Syncytial Virus Fusion Protein.

Viruses 2019 07 8;11(7). Epub 2019 Jul 8.

National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China.

Background: To date, there is no licensed vaccine available to prevent respiratory syncytial virus (RSV) infection. The valuable pre-fusion conformation of the fusion protein (pre-F) is prone to lose high neutralizing antigenic sites. The goals of this study were to stabilize pre-F protein by fixatives and try to find the possibility of developing an inactivated RSV vaccine. Read More

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Epitope-Specific Serological Assays for RSV: Conformation Matters.

Vaccines (Basel) 2019 Feb 23;7(1). Epub 2019 Feb 23.

Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in children and older adults. An effective vaccine must elicit neutralizing antibodies targeting the RSV fusion (F) protein, which exists in two major conformations, pre-fusion (pre-F) and post-fusion (post-F). Although 50% of the surface is shared, pre-F contains highly neutralization-sensitive antigenic sites not present on post-F. Read More

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February 2019

Comparison of Immune Responses to Different Versions of VLP Associated Stabilized RSV Pre-Fusion F Protein.

Vaccines (Basel) 2019 Feb 15;7(1). Epub 2019 Feb 15.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Efforts to develop a vaccine for respiratory syncytial virus (RSV) have primarily focused on the RSV fusion protein. The pre-fusion conformation of this protein induces the most potent neutralizing antibodies and is the focus of recent efforts in vaccine development. Following the first identification of mutations in the RSV F protein (DS-Cav1 mutant protein) that stabilized the pre-fusion conformation, other mutant stabilized pre-fusion F proteins have been described. Read More

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February 2019

Effect of Previous Respiratory Syncytial Virus Infection on Murine Immune Responses to F and G Protein-Containing Virus-Like Particles.

J Virol 2019 05 17;93(9). Epub 2019 Apr 17.

Department of Microbiology and Physiological Systems Program in Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Most individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein-containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV-naive animals. Read More

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Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness.

J Infect Dis 2019 01;219(1):59-67

Department of Medicine, University of Washington, Seattle.

Background: Transplacental respiratory syncytial virus (RSV) antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI). Read More

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January 2019

Regulatory Role of the Morbillivirus Attachment Protein Head-to-Stalk Linker Module in Membrane Fusion Triggering.

J Virol 2018 09 29;92(18). Epub 2018 Aug 29.

Division of Experimental and Clinical Research, DCR-VPH, Vetsuisse Faculty, University of Bern, Bern, Switzerland

Morbillivirus (e.g., measles virus [MeV] and canine distemper virus [CDV]) host cell entry is coordinated by two interacting envelope glycoproteins, namely, an attachment (H) protein and a fusion (F) protein. Read More

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September 2018

Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches.

Eur J Clin Microbiol Infect Dis 2018 Oct 6;37(10):1817-1827. Epub 2018 Jun 6.

Biomedical Research Center, Qatar University, 2713, Doha, Qatar.

Respiratory syncytial virus continues to pose a serious threat to the pediatric populations worldwide. With a genomic makeup of 15,200 nucleotides, the virus encodes for 11 proteins serving as envelope spikes, inner envelope proteins, and non-structural and ribonucleocapsid complexes. The fusion (F) and attachment (G) surface glycoproteins are the key targets for neutralizing antibodies. Read More

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October 2018

Efficacy of a respiratory syncytial virus vaccine candidate in a maternal immunization model.

Nat Commun 2018 05 15;9(1):1904. Epub 2018 May 15.

Department of Microbiology and Physiological Systems, Program of Immunology and Microbiology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. Read More

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Five Residues in the Apical Loop of the Respiratory Syncytial Virus Fusion Protein F Subunit Are Critical for Its Fusion Activity.

J Virol 2018 08 17;92(15). Epub 2018 Jul 17.

The Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, USA

The respiratory syncytial virus (RSV) fusion (F) protein is a trimeric, membrane-anchored glycoprotein capable of mediating both virus-target cell membrane fusion to initiate infection and cell-cell fusion, even in the absence of the attachment glycoprotein. The F protein is initially expressed in a precursor form, whose functional capabilities are activated by proteolysis at two sites between the F and F subunits. This cleavage results in expression of the metastable and high-energy prefusion conformation. Read More

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Playful pigs: Evidence of consistency and change in play depending on litter and developmental stage.

Appl Anim Behav Sci 2018 Jan;198:36-43

SRUC, West Mains Road, Edinburgh, EH9 3JG, United Kingdom.

Play behaviour in pre-weaned piglets has previously been shown to vary consistently between litters. This study aimed to determine if these pre-weaning litter differences in play behaviour were also consistent in the post-weaning period. Seven litters of commercially bred piglets were raised in a free farrowing system (PigSAFE) and weaned at 28 days post-farrowing (+/-2 days). Read More

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January 2018

Inferior immunogenicity and efficacy of respiratory syncytial virus fusion protein-based subunit vaccine candidates in aged versus young mice.

PLoS One 2017 28;12(11):e0188708. Epub 2017 Nov 28.

Department of Infectious Diseases/Vaccines, MedImmune, Gaithersburg, Maryland, United States of America.

Respiratory syncytial virus (RSV) is recognized as an important cause of lower and upper respiratory tract infections in older adults, and a successful vaccine would substantially lower morbidity and mortality in this age group. Recently, two vaccine candidates based on soluble purified glycoprotein F (RSV F), either alone or adjuvanted with glucopyranosyl lipid A formulated in a stable emulsion (GLA-SE), failed to reach their primary endpoints in clinical efficacy studies, despite demonstrating the desired immunogenicity profile and efficacy in young rodent models. Here, one of the RSV F vaccine candidates (post-fusion conformation, RSV post-F), and a stabilized pre-fusion form of RSV F (RSV pre-F, DS-Cav1) were evaluated in aged BALB/c mice. Read More

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December 2017

Neuroprotective Effects of Fasudil, a Rho-Kinase Inhibitor, After Spinal Cord Ischemia and Reperfusion in Rats.

Anesth Analg 2018 03;126(3):815-823

From the Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita, Akita, Japan.

Background: Excessive Rho/Rho-kinase pathway activation occurs subsequent to stroke. We examined the neuroprotective effects of pre- and posttreatment with fasudil (a Rho-kinase inhibitor) in a rat transient spinal cord ischemia-reperfusion model under normothermic conditions.

Methods: After approval by our animal research committee, male Sprague-Dawley rats were assigned to 1 of 6 groups: pre- and postcontrol (C); pre- and postfasudil (F); and pre- and postsham (S). Read More

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