Materiały źródłowe

• #1 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  Since the discovery of respiratory syncytial virus (RSV, originally called Chimpanzee Coryza Agent) in 1956, much has been learned about its pathogenesis and the impact of RSV disease in humans. […] The structure of postfusion F (postF) was determined in 2011. PostF is highly stable and displays known sites of recognition for neutralizing antibodies including palivizumab and its more potent derivative motavizumab. […] Determination of the preF structure, and the demonstration that vaccines retaining the preF structure preserved neutralization-sensitive epitopes and elicited supranormal levels of neutralizing activity was a game changer. […] The limited immunogenicity and efficacy of many prior vaccines can be linked to the presentation of postF lacking the most critical targets of vulnerability.

• #2 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease, especially in young children. […] In the last two decades, our understanding of the pathogenesis and immunopathology of RSV have continued to evolve, leading to significant advancements in RSV prevention strategies. […] The ERD phenomenon has since been studied extensively and is believed, in part, to be secondary to an exaggerated memory Th2 response, poor antibody affinity maturation, inadequate toll receptor signaling, and a low CD8 T-cell response. […] As our understanding of RSV structural biology and the mechanism of action has continued to evolve, there have been many advancements in RSV prevention strategies. […] RSV has several surface proteins, with two main glycoproteins as targets for immunization: the fusion (F) and attachment (G) proteins. Both are crucial for infectivity and viral pathogenesis.

• #3 Respiratory Syncytial Virus (RSV): The Disease, Vaccines & Monoclonal Antibody | Children’s Hospital of Philadelphia

  https://www.chop.edu/vaccine-education-center/vaccine-details/rsv-vaccine-monoclonal-antibody

  RSV is a virus in the Paramyxoviridae family, which is also the family of mumps and measles viruses. However, the three viruses are different enough that they are more like cousins than siblings. […] RSV was first isolated in the mid-1950s. It replicates in the cells that line the nose, large breathing tubes (causing bronchitis), small breathing tubes (causing bronchiolitis), and lungs (causing pneumonia). Sometimes it can also cause an infection of the voice box (called croup). As the virus replicates, it disrupts this lining. When this disruption is coupled with immune responses that cause inflammation and mucus production, the infected persons airways become narrower and fill with excess mucus, cell debris and fluid. […] Two of the RSV vaccines available for adults (Arexvy made by GSK [formerly GlaxoSmithKline] and Abrysvo made by Pfizer) are made of a single surface protein from the virus, called protein F. The gene for protein F is added to cells in the lab, so that as the cells grow, the protein is made too. It is then purified to remove the growth reagents and cellular debris.

• #4 Respiratory syncytial virus (RSV) | The Australian Immunisation Handbook

  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/respiratory-syncytial-virus-rsv

  RSV has an incubation period of 2–8 days. […] RSV infects cells lining the respiratory tract, including the small airways within the lung. Infected respiratory cells eventually die, causing an increase in mucus and small airway obstruction. This presents as lower respiratory tract infection. […] Severity of infection may be affected by very young or very old age, the presence of certain medical conditions, host immune response, and viral factors. […] Previous natural infection does not confer longstanding immunity and reinfection is common. Maternally derived antibody from vaccination or previous infection appears to reduce the risk of infection in young infants during the first few months of life.

• #5 Respiratory syncytial virus (RSV) | The Australian Immunisation Handbook

  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/respiratory-syncytial-virus-rsv

  RSV has an incubation period of 2–8 days. […] RSV infects cells lining the respiratory tract, including the small airways within the lung. Infected respiratory cells eventually die, causing an increase in mucus and small airway obstruction. This presents as lower respiratory tract infection. […] Severity of infection may be affected by very young or very old age, the presence of certain medical conditions, host immune response, and viral factors. […] Previous natural infection does not confer longstanding immunity and reinfection is common. Maternally derived antibody from vaccination or previous infection appears to reduce the risk of infection in young infants during the first few months of life.

• #6 RSV Disease Overview | GSK US Medical Affairs

  https://gskusmedicalaffairs.com/vaccines/respiratory-syncytial-virus/rsv-disease-overview/

  RSV replicates almost exclusively in apical ciliated epithelial cells. […] RSV causes a neutrophil-intensive inflammation of the airways. […] The degree of inflammation correlates with severity of infection. […] Lower airway obstructions are caused by cellular inclusions consisting of mucus, DNA, and cell debris that mainly derives from this neutrophil infiltration. […] RSV infection can also be accompanied by eosinophilia, which is particularly marked in the most severe cases. […] Neutralizing antibodies (nAbs) help prevent RSV infection through the inhibition of viral replication. nAbs inhibit the entry and spread of RSV in the human airway epithelium. […] RSV specific T-cell response reduces disease severity through promotion of viral clearance.

• #7 RSV Disease Overview | GSK US Medical Affairs

  https://gskusmedicalaffairs.com/vaccines/respiratory-syncytial-virus/rsv-disease-overview/

  RSV replicates almost exclusively in apical ciliated epithelial cells. […] RSV causes a neutrophil-intensive inflammation of the airways. […] The degree of inflammation correlates with severity of infection. […] Lower airway obstructions are caused by cellular inclusions consisting of mucus, DNA, and cell debris that mainly derives from this neutrophil infiltration. […] RSV infection can also be accompanied by eosinophilia, which is particularly marked in the most severe cases. […] Neutralizing antibodies (nAbs) help prevent RSV infection through the inhibition of viral replication. nAbs inhibit the entry and spread of RSV in the human airway epithelium. […] RSV specific T-cell response reduces disease severity through promotion of viral clearance.

• #8 RSV Disease Overview | GSK US Medical Affairs

  https://gskusmedicalaffairs.com/vaccines/respiratory-syncytial-virus/rsv-disease-overview/

  RSV replicates almost exclusively in apical ciliated epithelial cells. […] RSV causes a neutrophil-intensive inflammation of the airways. […] The degree of inflammation correlates with severity of infection. […] Lower airway obstructions are caused by cellular inclusions consisting of mucus, DNA, and cell debris that mainly derives from this neutrophil infiltration. […] RSV infection can also be accompanied by eosinophilia, which is particularly marked in the most severe cases. […] Neutralizing antibodies (nAbs) help prevent RSV infection through the inhibition of viral replication. nAbs inhibit the entry and spread of RSV in the human airway epithelium. […] RSV specific T-cell response reduces disease severity through promotion of viral clearance.

• #9 RSV Disease Overview | GSK US Medical Affairs

  https://gskusmedicalaffairs.com/vaccines/respiratory-syncytial-virus/rsv-disease-overview/

  RSV replicates almost exclusively in apical ciliated epithelial cells. […] RSV causes a neutrophil-intensive inflammation of the airways. […] The degree of inflammation correlates with severity of infection. […] Lower airway obstructions are caused by cellular inclusions consisting of mucus, DNA, and cell debris that mainly derives from this neutrophil infiltration. […] RSV infection can also be accompanied by eosinophilia, which is particularly marked in the most severe cases. […] Neutralizing antibodies (nAbs) help prevent RSV infection through the inhibition of viral replication. nAbs inhibit the entry and spread of RSV in the human airway epithelium. […] RSV specific T-cell response reduces disease severity through promotion of viral clearance.

• #10 RSV Disease Overview | GSK US Medical Affairs

  https://gskusmedicalaffairs.com/vaccines/respiratory-syncytial-virus/rsv-disease-overview/

  RSV replicates almost exclusively in apical ciliated epithelial cells. […] RSV causes a neutrophil-intensive inflammation of the airways. […] The degree of inflammation correlates with severity of infection. […] Lower airway obstructions are caused by cellular inclusions consisting of mucus, DNA, and cell debris that mainly derives from this neutrophil infiltration. […] RSV infection can also be accompanied by eosinophilia, which is particularly marked in the most severe cases. […] Neutralizing antibodies (nAbs) help prevent RSV infection through the inhibition of viral replication. nAbs inhibit the entry and spread of RSV in the human airway epithelium. […] RSV specific T-cell response reduces disease severity through promotion of viral clearance.

• #11 Respiratory syncytial virus (RSV) | The Australian Immunisation Handbook

  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/respiratory-syncytial-virus-rsv

  RSV has an incubation period of 2–8 days. […] RSV infects cells lining the respiratory tract, including the small airways within the lung. Infected respiratory cells eventually die, causing an increase in mucus and small airway obstruction. This presents as lower respiratory tract infection. […] Severity of infection may be affected by very young or very old age, the presence of certain medical conditions, host immune response, and viral factors. […] Previous natural infection does not confer longstanding immunity and reinfection is common. Maternally derived antibody from vaccination or previous infection appears to reduce the risk of infection in young infants during the first few months of life.

• #12 Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada, CCDR 46(4) – Canada.ca

  https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2020-46/issue-4-april-2-2020/article-1-challenges-developing-vaccine-respiratory-syncytial-virus.html

  A vaccine for respiratory syncytial virus (RSV) has been actively sought for over 60 years due to the health impacts of RSV disease in infants, but currently the only available preventive measure in Canada and elsewhere is limited to passive immunization for high-risk infants and children with a monoclonal antibody. […] RSV vaccine development has faced many challenges, including vaccine-induced enhancement of RSV disease in infants. […] A shadow was cast over vaccine development in the 1960s when a formalin-inactivated RSV (FI-RSV) vaccine was tested in seronegative children, that is, they were naive to RSV antigens. Instead of inducing protection, immunization resulted in enhanced respiratory disease (ERD) upon subsequent RSV infection, leading to two deaths. […] The key for vaccine development is to bolster immune responses, despite the dampening effect of RSV, to achieve the aims of the vaccine program: humoral responses may be targeted to prevent infection and cellular responses may be augmented to prevent severe disease.

• #13 Respiratory syncytial virus vaccine – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus_vaccine

  A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine that protects against respiratory syncytial virus. […] Attempts to develop an RSV vaccine began in the 1960s with an unsuccessful inactivated vaccine developed by exposing the RSV virus to formalin (formalin-inactivated RSV (FI-RSV)). This vaccine induced vaccine-associated enhanced respiratory disease, in which children who had not previously been exposed to RSV and were subsequently vaccinated would develop severe RSV disease if exposed to the virus itself, including fever, wheezing, and bronchopneumonia. […] A 2013 study detailed the crystal structure of the RSV fusion (F) protein and how its stability could be improved. This provided the basis for finding the most effective F protein constructs, which are used in RSV vaccines.

• #14 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  The changing landscape for vaccines and mAbs curated by PATH, and a recent comprehensive review detailing all candidates being tested in humans provide broader perspectives that are not covered by this review. […] The RSV vaccine field encountered tragedy shortly after discovery of the virus. Based on technology of the time, a formalin-inactivated (FI) RSV candidate was the first to be tested. […] The unexpected failure of FI-RSV made developers balk and approach testing, particularly in antigen-nave infants, with a high degree of caution. […] A major challenge for this approach has been balancing attenuation and immunogenicity. […] The F protein undergoes a dramatic and irreversible conformational transformation to postF during fusion, a substantial portion of the protein remains relatively unchanged such that four described antigenic sites (I, II, III, IV) are displayed on both forms of the protein. […] Therefore, to elicit the most potent antibodies and in turn, confer the most protection, F-based vaccines need to retain antigenic sites and V.

• #15 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  The changing landscape for vaccines and mAbs curated by PATH, and a recent comprehensive review detailing all candidates being tested in humans provide broader perspectives that are not covered by this review. […] The RSV vaccine field encountered tragedy shortly after discovery of the virus. Based on technology of the time, a formalin-inactivated (FI) RSV candidate was the first to be tested. […] The unexpected failure of FI-RSV made developers balk and approach testing, particularly in antigen-nave infants, with a high degree of caution. […] A major challenge for this approach has been balancing attenuation and immunogenicity. […] The F protein undergoes a dramatic and irreversible conformational transformation to postF during fusion, a substantial portion of the protein remains relatively unchanged such that four described antigenic sites (I, II, III, IV) are displayed on both forms of the protein. […] Therefore, to elicit the most potent antibodies and in turn, confer the most protection, F-based vaccines need to retain antigenic sites and V.

• #16 RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004757

  There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. […] However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. […] Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. […] A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF- was necessary to mediate airway obstruction and weight loss. […] Our studies demonstrate for the first time that distinct subsets of CD4 T cells orchestrate individual disease parameters associated with FI-RSV VED.

• #17

  https://link.springer.com/article/10.1007/s12026-007-0071-6

  In a series of vaccine trials conducted in the 1960s, a FI-RSV vaccine was administered to children. Surprisingly, 80% of the vaccinated children experienced serious disease and were hospitalized after acquiring a natural RSV infection, as compared to only 5% of a control vaccine group. […] Histological analysis of the lungs of the 2 children who tragically died revealed extensive mononuclear cell infiltration including pulmonary eosinophilia. […] In the 40+ years since the FI-RSV vaccine failure, much effort has been placed into gaining a better understanding of the immunological mechanisms that led to the enhanced disease experienced by the vaccinated children. […] RSV infection of FI-RSV-vaccinated BALB/c mice results in pulmonary eosinophilia that mimics the lung pathology observed in the FI-RSV vaccinated children.

• #18 RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004757

  There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. […] However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. […] Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. […] A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF- was necessary to mediate airway obstruction and weight loss. […] Our studies demonstrate for the first time that distinct subsets of CD4 T cells orchestrate individual disease parameters associated with FI-RSV VED.

• #19 RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004757

  There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. […] However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. […] Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. […] A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF- was necessary to mediate airway obstruction and weight loss. […] Our studies demonstrate for the first time that distinct subsets of CD4 T cells orchestrate individual disease parameters associated with FI-RSV VED.

• #20 RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004757

  Therefore, it remains unclear if eosinophils directly contribute to the severe immunopathology associated with FI-RSV ERD. […] Our results show that a Th2-biased immune response is necessary to mediate airway hyperreactivity and mucus hypersecretion disease parameters. In contrast, the Th1-associated cytokine TNF- was found to be critical for the induction of airway obstruction and weight loss associated with FI-RSV VED. […] Our results show that CD4 T cells are necessary to orchestrate an immune response that mediates all facets of disease associated with FI-RSV VED.

• #21

  https://link.springer.com/article/10.1007/s12026-007-0071-6

  This suggests that the immunized children were primed for a Th2 immune response by the vaccine. […] FI-RSV-vaccinated mice challenged with RSV exhibit increased levels of the Th2-associated cytokines IL-5, IL-4, IL-13, and the chemokine eotaxin. […] Although the production of Th2 cytokines is only correlative with disease, many studies have shown that Th2 cytokines are necessary for the development of pulmonary eosinophilia upon RSV challenge of FI-RSV-vaccinated mice. […] Thus, it is apparent that Th2 cytokines are essential for the development of pulmonary eosinophilia in the FI-RSV vaccine model. […] In addition to the T cell response, other factors contribute to FI-RSV vaccine-enhanced disease. […] Anti-RSV antibodies induced following FI-RSV vaccination have been shown to form immune complexes that may promote disease.

• #22

  https://link.springer.com/article/10.1007/s12026-007-0071-6

  This suggests that the immunized children were primed for a Th2 immune response by the vaccine. […] FI-RSV-vaccinated mice challenged with RSV exhibit increased levels of the Th2-associated cytokines IL-5, IL-4, IL-13, and the chemokine eotaxin. […] Although the production of Th2 cytokines is only correlative with disease, many studies have shown that Th2 cytokines are necessary for the development of pulmonary eosinophilia upon RSV challenge of FI-RSV-vaccinated mice. […] Thus, it is apparent that Th2 cytokines are essential for the development of pulmonary eosinophilia in the FI-RSV vaccine model. […] In addition to the T cell response, other factors contribute to FI-RSV vaccine-enhanced disease. […] Anti-RSV antibodies induced following FI-RSV vaccination have been shown to form immune complexes that may promote disease.

• #23

  https://link.springer.com/article/10.1007/s12026-007-0071-6

  This suggests that the immunized children were primed for a Th2 immune response by the vaccine. […] FI-RSV-vaccinated mice challenged with RSV exhibit increased levels of the Th2-associated cytokines IL-5, IL-4, IL-13, and the chemokine eotaxin. […] Although the production of Th2 cytokines is only correlative with disease, many studies have shown that Th2 cytokines are necessary for the development of pulmonary eosinophilia upon RSV challenge of FI-RSV-vaccinated mice. […] Thus, it is apparent that Th2 cytokines are essential for the development of pulmonary eosinophilia in the FI-RSV vaccine model. […] In addition to the T cell response, other factors contribute to FI-RSV vaccine-enhanced disease. […] Anti-RSV antibodies induced following FI-RSV vaccination have been shown to form immune complexes that may promote disease.

• #24 Respiratory syncytial virus vaccine – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus_vaccine

  A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine that protects against respiratory syncytial virus. […] Attempts to develop an RSV vaccine began in the 1960s with an unsuccessful inactivated vaccine developed by exposing the RSV virus to formalin (formalin-inactivated RSV (FI-RSV)). This vaccine induced vaccine-associated enhanced respiratory disease, in which children who had not previously been exposed to RSV and were subsequently vaccinated would develop severe RSV disease if exposed to the virus itself, including fever, wheezing, and bronchopneumonia. […] A 2013 study detailed the crystal structure of the RSV fusion (F) protein and how its stability could be improved. This provided the basis for finding the most effective F protein constructs, which are used in RSV vaccines.

• #25 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  The changing landscape for vaccines and mAbs curated by PATH, and a recent comprehensive review detailing all candidates being tested in humans provide broader perspectives that are not covered by this review. […] The RSV vaccine field encountered tragedy shortly after discovery of the virus. Based on technology of the time, a formalin-inactivated (FI) RSV candidate was the first to be tested. […] The unexpected failure of FI-RSV made developers balk and approach testing, particularly in antigen-nave infants, with a high degree of caution. […] A major challenge for this approach has been balancing attenuation and immunogenicity. […] The F protein undergoes a dramatic and irreversible conformational transformation to postF during fusion, a substantial portion of the protein remains relatively unchanged such that four described antigenic sites (I, II, III, IV) are displayed on both forms of the protein. […] Therefore, to elicit the most potent antibodies and in turn, confer the most protection, F-based vaccines need to retain antigenic sites and V.

• #26 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  Since the discovery that the F protein has two conformational forms, namely “pre-fusion F” (preF) and “post-fusion F” (postF), and the understanding that the preF conformation induces higher-potency neutralizing antibodies, it has become the preferred target for RSV-specific interventions. […] The current RSV vaccine candidates can be divided into live-attenuated (LAV) or chimeric vaccines, as well as protein-based, recombinant-vector-based, and nucleic-acid-based vaccines.

• #27 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  Since the discovery of respiratory syncytial virus (RSV, originally called Chimpanzee Coryza Agent) in 1956, much has been learned about its pathogenesis and the impact of RSV disease in humans. […] The structure of postfusion F (postF) was determined in 2011. PostF is highly stable and displays known sites of recognition for neutralizing antibodies including palivizumab and its more potent derivative motavizumab. […] Determination of the preF structure, and the demonstration that vaccines retaining the preF structure preserved neutralization-sensitive epitopes and elicited supranormal levels of neutralizing activity was a game changer. […] The limited immunogenicity and efficacy of many prior vaccines can be linked to the presentation of postF lacking the most critical targets of vulnerability.

• #28 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  Since the discovery of respiratory syncytial virus (RSV, originally called Chimpanzee Coryza Agent) in 1956, much has been learned about its pathogenesis and the impact of RSV disease in humans. […] The structure of postfusion F (postF) was determined in 2011. PostF is highly stable and displays known sites of recognition for neutralizing antibodies including palivizumab and its more potent derivative motavizumab. […] Determination of the preF structure, and the demonstration that vaccines retaining the preF structure preserved neutralization-sensitive epitopes and elicited supranormal levels of neutralizing activity was a game changer. […] The limited immunogenicity and efficacy of many prior vaccines can be linked to the presentation of postF lacking the most critical targets of vulnerability.

• #29 The road to approved vaccines for respiratory syncytial virus | npj Vaccines

  https://www.nature.com/articles/s41541-023-00734-7

  Since the discovery of respiratory syncytial virus (RSV, originally called Chimpanzee Coryza Agent) in 1956, much has been learned about its pathogenesis and the impact of RSV disease in humans. […] The structure of postfusion F (postF) was determined in 2011. PostF is highly stable and displays known sites of recognition for neutralizing antibodies including palivizumab and its more potent derivative motavizumab. […] Determination of the preF structure, and the demonstration that vaccines retaining the preF structure preserved neutralization-sensitive epitopes and elicited supranormal levels of neutralizing activity was a game changer. […] The limited immunogenicity and efficacy of many prior vaccines can be linked to the presentation of postF lacking the most critical targets of vulnerability.

• #30 RSV vaccines: the latest success story – IAVI

  http://www.iavi.org/iavi-report/rsv-vaccines-the-latest-success-story/

  The goal then was to use structure-based design to engineer amino acid substitutions into the F protein that help lock it in the prefusion state and prevent the conformational change from occurring. […] We knew that all the antibodies to the prefusion F protein bound to the apex. This was a novel site that nobody had seen before, in part because nobody had identified the prefusion F structure, and this is the region that completely refolds into a different conformation in the postfusion form so immunizing with postfusion F is never going to elicit these antibodies. […] Weve learned a lot of lessons from RSV, but they dont help overcome the issues plaguing HIV vaccine development. When I joined Peter Kwongs lab at the VRC, the whole lab was focused on HIV vaccine design and structure-based vaccine design, and I thought we were coming up with cool ideas for protein stabilization and epitope scaffolding. But nothing worked.

• #31 RSV vaccines: the latest success story – IAVI

  http://www.iavi.org/iavi-report/rsv-vaccines-the-latest-success-story/

  The goal then was to use structure-based design to engineer amino acid substitutions into the F protein that help lock it in the prefusion state and prevent the conformational change from occurring. […] We knew that all the antibodies to the prefusion F protein bound to the apex. This was a novel site that nobody had seen before, in part because nobody had identified the prefusion F structure, and this is the region that completely refolds into a different conformation in the postfusion form so immunizing with postfusion F is never going to elicit these antibodies. […] Weve learned a lot of lessons from RSV, but they dont help overcome the issues plaguing HIV vaccine development. When I joined Peter Kwongs lab at the VRC, the whole lab was focused on HIV vaccine design and structure-based vaccine design, and I thought we were coming up with cool ideas for protein stabilization and epitope scaffolding. But nothing worked.

• #32 A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism | Nature Communications

  https://www.nature.com/articles/ncomms9143

  To stabilize the soluble recombinant RSV F ectodomain, several RSV F variants were designed with different modifications. […] To preserve the protein in the prefusion conformation, we wanted to prevent the transition to the postfusion conformation by stabilizing the regions between the secondary structural elements that assembled into a long coiled-coil during the transformation from pre- to postfusion RSV F. […] The combination of substitutions N67I and S215P showed a clear additive effect on expression levels and also on stability of prefusion F protein. The high expression and prefusion stability agree with proper folding that has passed cellular quality control. […] The structural insights and stabilization strategies presented here produced a prefusion RSV F protein that was stable on storage at 4C for more than a year and was also heat stable, which is an important requirement for vaccine development.

• #33 A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism | Nature Communications

  https://www.nature.com/articles/ncomms9143

  RSV F fuses the viral and host cell membranes by irreversible protein refolding from the labile prefusion conformation to the stable postfusion conformation. Structures of both conformations have been determined for RSV F, as well as for the fusion proteins from related paramyxoviruses, providing insight into the mechanism of this complex fusion machine. […] Most in vitro RSV neutralizing antibodies in human sera are directed against the prefusion conformation, but due to its instability the prefusion conformation has a propensity to prematurely refold into the stable postfusion conformation, both in solution and on the surface of the virions. The stabilization of the RSV F protein has recently been achieved by the introduction of a disulphide bond between residues 155 and 290, introduction of two cavity-filling substitutions at positions 190 and 207, and attachment of a heterologous trimerization motif to the C terminus of HRB. These modifications led to the generation of a stable prefusion molecule with modest expression levels, but excellent immunogenicity in mice and macaques.

• #34 A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism | Nature Communications

  https://www.nature.com/articles/ncomms9143

  Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion RSV F elicits neutralizing antibodies in cotton rats and induces complete protection against viral challenge. Moreover, the structural and biochemical analysis of the prefusion variants suggests a function for p27, the excised segment that precedes the fusion peptide in the polypeptide chain.

• #35 A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism | Nature Communications

  https://www.nature.com/articles/ncomms9143

  To stabilize the soluble recombinant RSV F ectodomain, several RSV F variants were designed with different modifications. […] To preserve the protein in the prefusion conformation, we wanted to prevent the transition to the postfusion conformation by stabilizing the regions between the secondary structural elements that assembled into a long coiled-coil during the transformation from pre- to postfusion RSV F. […] The combination of substitutions N67I and S215P showed a clear additive effect on expression levels and also on stability of prefusion F protein. The high expression and prefusion stability agree with proper folding that has passed cellular quality control. […] The structural insights and stabilization strategies presented here produced a prefusion RSV F protein that was stable on storage at 4C for more than a year and was also heat stable, which is an important requirement for vaccine development.

• #36 A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism | Nature Communications

  https://www.nature.com/articles/ncomms9143

  To stabilize the soluble recombinant RSV F ectodomain, several RSV F variants were designed with different modifications. […] To preserve the protein in the prefusion conformation, we wanted to prevent the transition to the postfusion conformation by stabilizing the regions between the secondary structural elements that assembled into a long coiled-coil during the transformation from pre- to postfusion RSV F. […] The combination of substitutions N67I and S215P showed a clear additive effect on expression levels and also on stability of prefusion F protein. The high expression and prefusion stability agree with proper folding that has passed cellular quality control. […] The structural insights and stabilization strategies presented here produced a prefusion RSV F protein that was stable on storage at 4C for more than a year and was also heat stable, which is an important requirement for vaccine development.

• #37 RSV Vaccines: Uses, Dosage, Side Effects, Warnings – Drugs.com

  https://www.drugs.com/rsv-vaccine.html

  Abrysvo (Pfizer), Arexvy (GSK), and mRESVIA (Moderna) are RSV vaccines that are used to prevent severe RSV symptoms in adults aged 60 years and older. […] The mechanism of action of RSV vaccines involves stimulating the immune system to make antibodies against the respiratory syncytial virus which helps prevent severe symptoms of lower respiratory tract disease and reduces the risk of hospitalization or death in at-risk patients. […] When pregnant, the RSV vaccine Abrysvo helps the mother’s body make antibodies to the virus that are then passed through the placenta to the unborn baby. This will help protect the baby up to 6 months old against lower respiratory tract disease caused by RSV. […] RSV vaccines help prevent severe lower respiratory tract disease and reduce the risk of hospitalization or death in higher-risk patients.

• #38 Respiratory syncytial virus vaccine – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus_vaccine

  RSVpreF (Abrysvo) is a bivalent recombinant protein subunit vaccine which consists of equal amounts of stabilized prefusion F antigens from the two major RSV subgroups: RSV A and RSV B. […] In April 2023, Pfizer published their interim results of their phase III study of a RSV vaccine for adults age 60 and older in over 34,000 participants. One dose of the vaccine was 67% efficacious in preventing infections with at least two symptoms and it was 86% effective against more severe disease, in people with three related symptoms. […] Mresvia is an mRNA vaccine that was studied in clinical trial NCT05127434. It was approved for medical use in the United States in May 2024.

• #39 Abrysvo (respiratory syncytial virus [RSV] vaccine) dosing, indications, interactions, adverse effects, and more

  https://reference.medscape.com/drug/abrysvo-respiratory-syncytial-virus-rsv-vaccine-4000347

  Vaccine composed of equal amounts of recombinant RSV prefusion F from subgroups A and B. […] Induces an immune response against RSV pre F that protects against lower respiratory tract disease caused by RSV.

• #40 HIGHLIGHTS OF PRESCRIBING INFORMATION

  https://labeling.pfizer.com/ShowLabeling.aspx?id=19589

  ABRYSVO induces an immune response against RSVpreF that protects against lower respiratory tract disease caused by RSV. […] Antibodies to RSV antigens from individuals vaccinated in pregnancy are transferred transplacentally to protect infants younger than 6 months of age against LRTD and severe LRTD caused by RSV.

• #41 Arexvy (RSV vaccine) to Prevent Lower Respiratory Tract Disease, USA

  https://www.clinicaltrialsarena.com/projects/arexvy-prevent-lower-respiratory-tract-disease/

  Arexvy is a first-of-its-kind adjuvanted respiratory syncytial virus (RSV) vaccine indicated as a preventive measure against lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 and older. […] Arexvy is a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with AS01E adjuvant. […] The vaccine provides adult immunisation by triggering an immune response against RSVpreF3, thus protecting against LRTD caused by RSV.

• #42 Arexvy (RSV vaccine) to Prevent Lower Respiratory Tract Disease, USA

  https://www.clinicaltrialsarena.com/projects/arexvy-prevent-lower-respiratory-tract-disease/

  Arexvy is a first-of-its-kind adjuvanted respiratory syncytial virus (RSV) vaccine indicated as a preventive measure against lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 and older. […] Arexvy is a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with AS01E adjuvant. […] The vaccine provides adult immunisation by triggering an immune response against RSVpreF3, thus protecting against LRTD caused by RSV.

• #43 News – Authorisation Recommended for Respiratory Syncytial Virus (RSV) Vaccine – Paul-Ehrlich-Institut

  https://www.pei.de/EN/newsroom/hp-news/2023/230428-authorisation-rsv-vaccine-recommended.html

  The vaccine product from GlaxoSmithKline Biologicals S.A. is intended for use in adults aged 60 years and older to protect against lower respiratory tract disease caused by respiratory syncytial virus (RSV) infection. […] Arexvy contains a genetically modified version of the RSV fusion protein (F) in a stabilised prefusion form (RSVPreF3). This protein is essential for an RSV infection to occur. The version of the protein contained in the vaccine acts as an antigen against which antibodies are formed by the immune system to protect against infection. […] The vaccine also contains the adjuvant AS01E, which enhances the immune response to the vaccine.

• #44 News – Authorisation Recommended for Respiratory Syncytial Virus (RSV) Vaccine – Paul-Ehrlich-Institut

  https://www.pei.de/EN/newsroom/hp-news/2023/230428-authorisation-rsv-vaccine-recommended.html

  The vaccine product from GlaxoSmithKline Biologicals S.A. is intended for use in adults aged 60 years and older to protect against lower respiratory tract disease caused by respiratory syncytial virus (RSV) infection. […] Arexvy contains a genetically modified version of the RSV fusion protein (F) in a stabilised prefusion form (RSVPreF3). This protein is essential for an RSV infection to occur. The version of the protein contained in the vaccine acts as an antigen against which antibodies are formed by the immune system to protect against infection. […] The vaccine also contains the adjuvant AS01E, which enhances the immune response to the vaccine.

• #45 Respiratory Syncytial Virus Prefusion F (RSVPreF3) Vaccine – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594261/

  The AS01 adjuvant contained in the RSVPreF3 vaccine is a liposomal formulation that combines 2 immunostimulants that are QS-21, extracted from the bark of the Quillaja saponaria tree, and MPL, a synthetic derivative of bacterial lipopolysaccharide (Salmonella Minnesota strain). The AS01 adjuvant enhances the immune response to the RSVPreF3 antigen by activating innate immune cells, inducing cytokine production, promoting antigen presentation, and stimulating humoral and cellular immunity. Moreover, the AS01 adjuvant also helps overcome the natural decline in immunity that accompanies aging by amplifying the magnitude and quality of the antibody response.

• #46

  https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx

  mRNA-1345 demonstrated vaccine efficacy of 83.7% against RSV lower respiratory tract disease, defined by 2 or more symptoms in older adults. […] mRNA-1345 is an investigational RSV vaccine that consists of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein. The vaccine uses the same lipid nanoparticles (LNPs) as in the Moderna COVID-19 vaccines. The F glycoprotein is on the surface of the virus and is required for infection by helping the virus to enter host cells. It exists in two states, prefusion and postfusion. The prefusion conformation is a significant target of potent neutralizing antibodies and is highly conserved across both RSV-A and RSV-B subtypes. […] The Phase 3 trial is part of a comprehensive clinical development program investigating the immunogenicity and safety of mRNA-1345.

• #47 mResvia (respiratory syncytial virus [RSV] vaccine, mRNA) dosing, indications, interactions, adverse effects, and more

  https://reference.medscape.com/drug/mresvia-respiratory-syncytial-virus-rsv-vaccine-mrna-4000422

  Vaccine induces immune response against RSV pre-F protein that protects against lower respiratory tract disease caused by RSV […] Vaccine formulated in lipid nanoparticles, which enable delivery of RNA into host cells to allow expression of the F glycoprotein is on the virus surface that is required for the virus to enter host cells […] It exists in 2 states, prefusion and postfusion; prefusion conformation is a significant target of potent neutralizing antibodies and is highly conserved across both RSV-A and RSV-B subtypes.

• #48 Respiratory Syncytial Virus (RSV): The Disease, Vaccines & Monoclonal Antibody | Children’s Hospital of Philadelphia

  https://www.chop.edu/vaccine-education-center/vaccine-details/rsv-vaccine-monoclonal-antibody

  Mresvia, made by Moderna, is an mRNA-based vaccine. The mRNA in the vaccine instructs a persons cells to produce the same antigen (protein F) that is contained in the protein-based vaccines. When the protein is made, our immune system recognizes it as foreign and mounts an immune response against it. This is similar to how the COVID-19 mRNA vaccines work as shown in this animation. […] The monoclonal antibody is one that can bind to the F protein on RSV, preventing the virus from binding to and entering cells. It is a type of antibody known as immunoglobulin G (IgG). This type of antibody is commonly found circulating in our blood. The gene for the IgG antibody is added to mammalian cells, so that when the cells reproduce in the lab, they also make the antibodies, which are then purified.

• #49 Should You Get an RSV Vaccine? > News > Yale Medicine

  https://www.yalemedicine.org/news/should-you-get-an-rsv-vaccine

  One turning point came with the investigation of an RSV protein called RSV fusion (F) that provided potent stimulation to the immune system research that paved the way to clinical trials showing positive results. […] Both the AREXVY and ABRYSVO vaccines for older adults use traditional platforms similar to a flu shot (and not to be confused with the mRNA technology introduced by Pfizer-BioNTech and Moderna to prevent COVID-19). These RSV vaccines work by introducing an inactivated RSV protein into the body, where it fuses to host cells and stimulates the immune system to recognize the actual RSV virus if/when it encounters it and help prevent severe disease. […] The third vaccine, mRESVIA, from Moderna, uses an mRNA platform, similar to the companys COVID vaccine. […] ABRYSVO, also approved in May 2023, showed an efficacy of almost 89% against LRTD involving at least three symptoms in the first year after vaccination, and 78.6% mid-way through a second season in the data presented to the FDA. LRTD symptoms include new or increased cough, wheezing, sputum (phlegm) production, shortness of breath, and/or tachypnea (abnormally rapid breathing). […] mRESVIA, was approved in May 2024 after Moderna provided trial clinical trial data showing an efficacy against LRTD of 83.7%. In June, the company reported that its vaccine had only 50% efficacy in preventing illness after 18 months.

• #50 RSV Vaccine Guidance for Older Adults | RSV | CDC

  https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/older-adults.html

  CDC recommends a single dose of RSV vaccine for older adults to help prevent serious RSV infection and hospitalization. […] Currently, CDC recommends only a single dose of RSV vaccine for all adults ages 75 and older and for adults ages 6074 with increased risk of severe RSV disease. Additional surveillance and evaluation activities are ongoing to determine whether adults might benefit from receiving additional RSV vaccine doses in the future. […] In studies of the real-world effectiveness of Arexvy during the 20232024 RSV season, the first since licensure of Arexvy, Arexvy was approximately 77% effective in preventing RSV-associated emergency department encounters and 83% effective in preventing RSV-associated hospitalizations in adults 60 and older. […] In studies of the real-world effectiveness of Abrysvo during the 20232024 RSV season, the first RSV season since licensure, Abrysvo was approximately 79% effective in preventing RSV-associated emergency department encounters and 73% effective in preventing RSV-associated hospitalizations in adults 60 and older.

• #51 European Commission authorises GSK’s Arexvy, the first respiratory syncytial virus (RSV) vaccine for older adults | GSK

  https://www.gsk.com/en-gb/media/press-releases/european-commission-authorises-gsk-s-arexvy-the-first-respiratory-syncytial-virus-rsv-vaccine-for-older-adults/

  GSK plc (LSE/NYSE: GSK) today announced that the European Commission has authorised Arexvy (respiratory syncytial virus vaccine, adjuvanted) for active immunisation for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in adults 60 years of age and older. […] The authorisation is based on GSKs landmark positive pivotal AReSVi-006 (Adult Respiratory Syncytial Virus) phase III trial data. In the trial, the vaccine showed statistically significant and clinically meaningful overall efficacy of 82.6% (96.95% CI, 57.994.1, 7 of 12,466 vs 40 of 12,494) against RSV-LRTD in adults aged 60 years and older, meeting the primary endpoint. […] RSV is a common contagious virus affecting the lungs and breathing passages. Older adults are at high risk for severe disease due in part to age-related decline in immunity. Older adults with underlying medical conditions are at even greater risk for severe disease. RSV can exacerbate conditions, including chronic obstructive pulmonary disease (COPD), asthma, and chronic heart failure and can lead to severe outcomes, such as pneumonia, hospitalisation, and death.

• #52 RSV Vaccine Guidance for Older Adults | RSV | CDC

  https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/older-adults.html

  CDC recommends a single dose of RSV vaccine for older adults to help prevent serious RSV infection and hospitalization. […] Currently, CDC recommends only a single dose of RSV vaccine for all adults ages 75 and older and for adults ages 6074 with increased risk of severe RSV disease. Additional surveillance and evaluation activities are ongoing to determine whether adults might benefit from receiving additional RSV vaccine doses in the future. […] In studies of the real-world effectiveness of Arexvy during the 20232024 RSV season, the first since licensure of Arexvy, Arexvy was approximately 77% effective in preventing RSV-associated emergency department encounters and 83% effective in preventing RSV-associated hospitalizations in adults 60 and older. […] In studies of the real-world effectiveness of Abrysvo during the 20232024 RSV season, the first RSV season since licensure, Abrysvo was approximately 79% effective in preventing RSV-associated emergency department encounters and 73% effective in preventing RSV-associated hospitalizations in adults 60 and older.

• #53 The Efficacy, Mechanism of Action for the RSV Vaccines

  https://www.contagionlive.com/view/the-efficacy-mechanism-of-action-for-the-rsv-vaccines

  In this second episode, Falsey and Walsh discuss the efficacy and mechanism of action of the various RSV vaccines. […] The FDA approval of the Moderna RSV vaccine, mRNA 1345 (mRESVIA), was based from the results of the phase 3 ConquerRSV trial, which demonstrated an 83.7% efficacy against infection.

• #54 Should You Get an RSV Vaccine? > News > Yale Medicine

  https://www.yalemedicine.org/news/should-you-get-an-rsv-vaccine

  One turning point came with the investigation of an RSV protein called RSV fusion (F) that provided potent stimulation to the immune system research that paved the way to clinical trials showing positive results. […] Both the AREXVY and ABRYSVO vaccines for older adults use traditional platforms similar to a flu shot (and not to be confused with the mRNA technology introduced by Pfizer-BioNTech and Moderna to prevent COVID-19). These RSV vaccines work by introducing an inactivated RSV protein into the body, where it fuses to host cells and stimulates the immune system to recognize the actual RSV virus if/when it encounters it and help prevent severe disease. […] The third vaccine, mRESVIA, from Moderna, uses an mRNA platform, similar to the companys COVID vaccine. […] ABRYSVO, also approved in May 2023, showed an efficacy of almost 89% against LRTD involving at least three symptoms in the first year after vaccination, and 78.6% mid-way through a second season in the data presented to the FDA. LRTD symptoms include new or increased cough, wheezing, sputum (phlegm) production, shortness of breath, and/or tachypnea (abnormally rapid breathing). […] mRESVIA, was approved in May 2024 after Moderna provided trial clinical trial data showing an efficacy against LRTD of 83.7%. In June, the company reported that its vaccine had only 50% efficacy in preventing illness after 18 months.

• #55 RSV Vaccine Guidance for Older Adults | RSV | CDC

  https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/older-adults.html

  Due to the recency of mResvia licensure, real-world vaccine effectiveness against RSV-associated hospitalization and other severe illness cannot yet be estimated. Vaccine efficacy data are available from one large phase 2/3 randomized, blinded placebo-controlled clinical trial in participants ages 60 and older. In this trial, efficacy of a single dose of mResvia against symptomatic RSV was approximately 80% during the first 4 months following vaccination and approximately 56% during the first 12 months after vaccination.

• #56

  https://link.springer.com/article/10.1007/s10096-018-3289-4

  Respiratory syncytial virus continues to pose a serious threat to the pediatric populations worldwide. The fusion (F) and attachment (G) surface glycoproteins are the key targets for neutralizing antibodies. The highly variable G with altered glycosylations and the conformational alternations of F create challenges for vaccine development. The metastable F protein is responsible for RSV-host cell fusion and thus infectivity. Novel antigenic sites were identified on this form following its stabilization and solving its crystal structure. Importantly, site displays neutralizing activity exceeding those of post-F-specific and shared antigenic sites, such as site II which is the target for Palivizumab therapeutic antibody. Induction of high neutralizing antibody responses by pre-F immunization in animal models promoted it as a major vaccine candidate. Since RSV infection is more serious at age extremities and in individuals with undermining health conditions, vaccines are being developed to target these populations. Infants below three months of age have a suppressive immune system, making vaccines immunogenicity weak. Therefore, a suggested strategy to protect newborns from RSV infection would be through passive immunity of maternal antibodies. Hence, pregnant women at their third trimester have been selected as an ideal target for vaccination with RSV pre-F vaccine. […] This review summarizes the different modes of RSV pathogenesis and hosts immune response to the infection, and illustrates on the latest updates of vaccine development and vaccination approaches.

• #57 RSV Vaccines: Uses, Dosage, Side Effects, Warnings – Drugs.com

  https://www.drugs.com/rsv-vaccine.html

  RSV vaccines Abrysvo (Pfizer), Arexvy (GSK), and mRESVIA (Moderna) are indicated for adults aged 60 years and older as they are at higher risk of severe RSV, which can lead to serious complications such as pneumonia and death. […] Abrysvo’s FDA approval also includes adults aged 18 through 59 years at high risk of LRTD from RSV and pregnant women from 32 through 36 weeks gestation. […] Abrysvo may be given in late pregnancy to help protect the baby when it is born and up until 6 months of age against severe LRTD caused by RSV.

• #58 HIGHLIGHTS OF PRESCRIBING INFORMATION

  https://labeling.pfizer.com/ShowLabeling.aspx?id=19589

  ABRYSVO induces an immune response against RSVpreF that protects against lower respiratory tract disease caused by RSV. […] Antibodies to RSV antigens from individuals vaccinated in pregnancy are transferred transplacentally to protect infants younger than 6 months of age against LRTD and severe LRTD caused by RSV.

• #59 Respiratory Syncytial Virus (RSV): The Disease, Vaccines & Monoclonal Antibody | Children’s Hospital of Philadelphia

  https://www.chop.edu/vaccine-education-center/vaccine-details/rsv-vaccine-monoclonal-antibody

  In clinical trials, a single dose of either protein-based RSV vaccine for adults prevented RSV infections associated with the lower respiratory tract in about 70 to 90 of 100 vaccine recipients. The mRNA-based RSV vaccine protected about 60 to 80 of 100 vaccine recipients against lower respiratory tract infections in clinical trials. […] Because infections of the lower respiratory tract suggest a more severe infection, preventing these types of infections means that these vaccines will likely reduce hospitalizations and deaths associated with RSV. […] In clinical trials, a single dose of the RSV vaccine administered during pregnancy reduced the risk of an RSV infection leading to hospitalization during the first six months of life in 57 of 100 infants born to vaccinated individuals. […] Yes. Babies who get nirsevimab are less likely to require medical intervention for an RSV infection, including going to the emergency room, being hospitalized, ending up in the intensive care unit or needing oxygen. The antibody product is estimated to prevent about 7 or 8 of every 10 babies who receive it from having severe RSV that requires these types of interventions.

• #60 Study details why phase 3 trial of GSK’s RSV vaccine for pregnant women was halted early | CIDRAP

  https://www.cidrap.umn.edu/respiratory-syncytial-virus-rsv/study-details-why-phase-3-trial-gsks-rsv-vaccine-pregnant-women-was

  A study today in the New England Journal of Medicine discusses a phase 3 randomized, controlled trial of GSK’s respiratory syncytial virus (RSV) vaccine in pregnant women that was stopped early owing to an increased risk of preterm birth. […] The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. […] „Despite many post hoc analyses, the authors were unable to identify a mechanism by which the receipt of RSVPreF3-Mat might have increased the risk of preterm birth,” they wrote. „However, given the findings of the present trial and the modest imbalance in the incidence of preterm birth in the phase 3 trial of the bivalent vaccine [Abryvso], postmarketing surveillance of the bivalent vaccine is warranted.”

• #61 Beyfortus (nirsevimab-alip) Mechanism of Action | Beyfortus®

  https://pro.campus.sanofi/us/products/beyfortus/mechanism-of-action

  Beyfortus is a recombinant human immunoglobulin G1 kappa (IgG1) monoclonal antibody (mAb) designed to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants. Unlike infection or vaccination, RSV antibody therapy does not stimulate the immune system. Instead, mAbs provide direct protection against disease, representing a form of passive immunization against RSV disease. Protection is typically at its peak in the weeks following administration of Beyfortus but diminishes gradually over time. […] […] Beyfortus is a protein-directed fusion inhibitor that provides long-acting passive immunity to RSV disease by binding to a conserved epitope on the RSV prefusion F protein, interfering with cellular membrane fusion, thus preventing viral entry into cells. […]

• #62 Beyfortus (nirsevimab-alip) Mechanism of Action | Beyfortus®

  https://pro.campus.sanofi/us/products/beyfortus/mechanism-of-action

  Beyfortus is a recombinant human immunoglobulin G1 kappa (IgG1) monoclonal antibody (mAb) designed to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants. Unlike infection or vaccination, RSV antibody therapy does not stimulate the immune system. Instead, mAbs provide direct protection against disease, representing a form of passive immunization against RSV disease. Protection is typically at its peak in the weeks following administration of Beyfortus but diminishes gradually over time. […] […] Beyfortus is a protein-directed fusion inhibitor that provides long-acting passive immunity to RSV disease by binding to a conserved epitope on the RSV prefusion F protein, interfering with cellular membrane fusion, thus preventing viral entry into cells. […]

• #63 Beyfortus (nirsevimab-alip) Mechanism of Action | Beyfortus®

  https://pro.campus.sanofi/us/products/beyfortus/mechanism-of-action

  Beyfortus is a recombinant human immunoglobulin G1 kappa (IgG1) monoclonal antibody (mAb) designed to prevent respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants. Unlike infection or vaccination, RSV antibody therapy does not stimulate the immune system. Instead, mAbs provide direct protection against disease, representing a form of passive immunization against RSV disease. Protection is typically at its peak in the weeks following administration of Beyfortus but diminishes gradually over time. […] […] Beyfortus is a protein-directed fusion inhibitor that provides long-acting passive immunity to RSV disease by binding to a conserved epitope on the RSV prefusion F protein, interfering with cellular membrane fusion, thus preventing viral entry into cells. […]

• #64 Beyfortus (nirsevimab-alip) Mechanism of Action | Beyfortus®

  https://pro.campus.sanofi/us/products/beyfortus/mechanism-of-action

  Upon infection, the RSV F protein, typically responsible for facilitating pH-independent viral membrane fusion with the host-cell plasma membrane, triggers the merging of adjacent cells when expressed on the cell surface. This membrane fusion process results in the formation of syncytia, large multinucleated structures that can induce epithelial lesions in the upper respiratory tract. Formation of syncytia (cell-cell fusion) is what gives RSV its characteristic name. […] […] Beyfortus RSV antibody therapy is long-acting due to a specially designed triple amino acid substitution (YTE) in its fragment crystallizable (Fc) region, increasing its affinity to the neonatal Fc receptor. This YTE substitution in the Fc segment of Beyfortus prolongs its serum half-life, and is designed to provide season-long protection that extends through 5 months after injection with a single intramuscular dose. Specifically, the YTE modification results in a long anti-RSV antibody half-life extension from 2128 days to 87117 days.

• #65 Respiratory Syncytial Virus (RSV): The Disease, Vaccines & Monoclonal Antibody | Children’s Hospital of Philadelphia

  https://www.chop.edu/vaccine-education-center/vaccine-details/rsv-vaccine-monoclonal-antibody

  In clinical trials, a single dose of either protein-based RSV vaccine for adults prevented RSV infections associated with the lower respiratory tract in about 70 to 90 of 100 vaccine recipients. The mRNA-based RSV vaccine protected about 60 to 80 of 100 vaccine recipients against lower respiratory tract infections in clinical trials. […] Because infections of the lower respiratory tract suggest a more severe infection, preventing these types of infections means that these vaccines will likely reduce hospitalizations and deaths associated with RSV. […] In clinical trials, a single dose of the RSV vaccine administered during pregnancy reduced the risk of an RSV infection leading to hospitalization during the first six months of life in 57 of 100 infants born to vaccinated individuals. […] Yes. Babies who get nirsevimab are less likely to require medical intervention for an RSV infection, including going to the emergency room, being hospitalized, ending up in the intensive care unit or needing oxygen. The antibody product is estimated to prevent about 7 or 8 of every 10 babies who receive it from having severe RSV that requires these types of interventions.

• #66 Researcher Identifies Adjuvant That Prevents Vaccine-Enhanced Respiratory Disease In RSV, Study Finds – Georgia State University News – Faculty, Institute for Biomedical Sciences, Press Releases, Research, University Research – Health & Wellness

  https://news.gsu.edu/2019/06/12/biomedical-sciences-researcher-identifies-adjuvant-that-prevents-vaccine-enhanced-respiratory-disease-in-rsv-study-finds/

  A unique adjuvant, a substance that enhances the body’s immune response to toxins and foreign matter, can prevent vaccine-enhanced respiratory disease, a sickness that has posed a major hurdle in vaccine development for respiratory syncytial virus (RSV), according to a study led by the Institute for Biomedical Sciences at Georgia State University. […] The study suggests that combining this adjuvant, which was created by the research team, with RSV vaccination might prime the body for protective immune responses and prevent inflammatory RSV disease after infection. […] This study investigated the effects of a unique adjuvant on vaccine-enhanced respiratory disease after infant and adult mice were vaccinated against RSV and exposed to the virus. […] The adjuvant was found to be effective in promoting the induction of protective antibodies, clearing the lungs of the virus after exposure to RSV and avoiding disease in lung tissue.

• #67 Researcher Identifies Adjuvant That Prevents Vaccine-Enhanced Respiratory Disease In RSV, Study Finds – Georgia State University News – Faculty, Institute for Biomedical Sciences, Press Releases, Research, University Research – Health & Wellness

  https://news.gsu.edu/2019/06/12/biomedical-sciences-researcher-identifies-adjuvant-that-prevents-vaccine-enhanced-respiratory-disease-in-rsv-study-finds/

  A unique adjuvant, a substance that enhances the body’s immune response to toxins and foreign matter, can prevent vaccine-enhanced respiratory disease, a sickness that has posed a major hurdle in vaccine development for respiratory syncytial virus (RSV), according to a study led by the Institute for Biomedical Sciences at Georgia State University. […] The study suggests that combining this adjuvant, which was created by the research team, with RSV vaccination might prime the body for protective immune responses and prevent inflammatory RSV disease after infection. […] This study investigated the effects of a unique adjuvant on vaccine-enhanced respiratory disease after infant and adult mice were vaccinated against RSV and exposed to the virus. […] The adjuvant was found to be effective in promoting the induction of protective antibodies, clearing the lungs of the virus after exposure to RSV and avoiding disease in lung tissue.

• #68 Researcher Identifies Adjuvant That Prevents Vaccine-Enhanced Respiratory Disease In RSV, Study Finds – Georgia State University News – Faculty, Institute for Biomedical Sciences, Press Releases, Research, University Research – Health & Wellness

  https://news.gsu.edu/2019/06/12/biomedical-sciences-researcher-identifies-adjuvant-that-prevents-vaccine-enhanced-respiratory-disease-in-rsv-study-finds/

  RSV subunit vaccination adjuvanted with a unique combination pathogen-recognizing receptor agonist might provide protection against RSV, preventing inflammatory RSV disease after infection. […] In another recent study published in the journal Antiviral Research, Kang found that an inactivated split RSV vaccine with a unique combination adjuvant was more effective in increasing immune responses and antibodies, lung viral clearance and preventing pulmonary tissue disease than an earlier form of the vaccine.

• #69 Vaccine Using Microneedle Patch With RSV Virus, Immune-Stimulating Compound Is Effective Against RSV – Georgia State University News – Faculty, Institute for Biomedical Sciences, Press Releases, Research, University Research – Health & Wellness

  https://news.gsu.edu/2018/12/17/vaccine-using-microneedle-patch-with-rsv-virus-immune-stimulating-compound-is-effective-against-rsv-study-finds/

  Skin vaccination using a microneedle patch that contains the inactivated respiratory syncytial virus (RSV) and a compound that stimulates immune responses to the virus has been found to enhance protection against this serious disease and reduce inflammation in the body after exposure to the virus, according to a study led by Georgia State University. […] The addition of the adjuvant to the microneedle patch significantly increased the vaccines ability to induce an immune response, clear the virus from the lungs of mice and prevent RSV inflammatory disease. […] Skin delivery of RSV vaccines with an appropriate adjuvant can be translational to the clinic, said Dr. Sang-Moo Kang, senior author of the study and professor in the Institute for Biomedical Sciences at Georgia State. […] Research interests: Influenza/RSV Vaccines, Immunity, Inflammation and Pathogenesis.

• #70 Vaccine Using Microneedle Patch With RSV Virus, Immune-Stimulating Compound Is Effective Against RSV – Georgia State University News – Faculty, Institute for Biomedical Sciences, Press Releases, Research, University Research – Health & Wellness

  https://news.gsu.edu/2018/12/17/vaccine-using-microneedle-patch-with-rsv-virus-immune-stimulating-compound-is-effective-against-rsv-study-finds/

  Skin vaccination using a microneedle patch that contains the inactivated respiratory syncytial virus (RSV) and a compound that stimulates immune responses to the virus has been found to enhance protection against this serious disease and reduce inflammation in the body after exposure to the virus, according to a study led by Georgia State University. […] The addition of the adjuvant to the microneedle patch significantly increased the vaccines ability to induce an immune response, clear the virus from the lungs of mice and prevent RSV inflammatory disease. […] Skin delivery of RSV vaccines with an appropriate adjuvant can be translational to the clinic, said Dr. Sang-Moo Kang, senior author of the study and professor in the Institute for Biomedical Sciences at Georgia State. […] Research interests: Influenza/RSV Vaccines, Immunity, Inflammation and Pathogenesis.

• #71 Pipeline – AstraZeneca

  https://www.astrazeneca.com/our-therapy-areas/pipeline.html

  IVX-A12 is a virus-like particle combination vaccine for the prevention of lower respiratory tract disease (LRTD) caused RSV and hMPV. […] mRNA VLP vaccine – Mechanism: mRNA-VLP vaccine […] Mechanism: pseudomonas Psl-PcrV bispecific mAb.

• #72 Pipeline – AstraZeneca

  https://www.astrazeneca.com/our-therapy-areas/pipeline.html

  IVX-A12 is a virus-like particle combination vaccine for the prevention of lower respiratory tract disease (LRTD) caused RSV and hMPV. […] mRNA VLP vaccine – Mechanism: mRNA-VLP vaccine […] Mechanism: pseudomonas Psl-PcrV bispecific mAb.

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