ArticlePathogens & immunity2019
Crystal Structure and Immunogenicity of the DS-Cav1-Stabilized Fusion Glycoprotein From Respiratory Syncytial Virus Subtype B.
Article in Pathogens & immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 18 citations in OpenAlex.
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- Nirsevimab for respiratory syncytial virus prevention: A comprehensive product review.Human vaccines & immunotherapeutics · 2026Review
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- Intranasal Delivery of an RSV A2-Derived Pre-F VLP Vaccine Induces Robust Mucosal and Systemic Immunity Against RSV B Strain Without Enhanced Disease.Immune network · 2026Article
- Enhanced Th1 Cellular Immunity Induced by an RSV-F mRNA Vaccine Rationally Designed Using NLP Algorithms.Vaccines · 2026Article
- Developing an eVLP mRNA vaccine for respiratory syncytial virus with enhanced pre-fusion targeting humoral responses.Journal of virology · 2025Article
- Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies.Cell reports · 2024Article
- Strategies of rational and structure-driven vaccine design for Arenaviruses.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2024Review
- Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.Infectious diseases and therapy · 2024Review
- Immunogenicity of a recombinant plant-produced respiratory syncytial virus F subunit vaccine in mice.Biotechnology reports (Amsterdam, Netherlands) · 2024Article
- Systematic computer-aided disulfide design as a general strategy to stabilize prefusion class I fusion proteins.Frontiers in immunology · 2024Article
- Respiratory syncytial virus infection and novel interventions.Nature reviews. Microbiology · 2023Review
- Respiratory Syncytial Virus Vaccines: A Review of the Candidates and the Approved Vaccines.Pathogens (Basel, Switzerland) · 2023Review
- The Efficiency of p27 Cleavage duringJournal of virology · 2023Article
- Article
- Cross-protective antibodies against common endemic respiratory viruses.Nature communications · 2023Article
- Identification of a DRB3*011:01-restricted CD4Frontiers in immunology · 2023Article
- A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.Frontiers in immunology · 2022Article
- SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.Cell reports · 2021Article
- Interprotomer disulfide-stabilized variants of the human metapneumovirus fusion glycoprotein induce high titer-neutralizing responses.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRespiratory syncytial virus (RSV) subtypes, A and B, co-circulate in annual epidemics and alternate in dominance. We have shown that a subtype A RSV fusion (F) glycoprotein, stabilized in its prefusion conformation by DS-Cav1 mutations, is a promising RSV-vaccine immunogen, capable of boosting RSV-neutralizing titers in healthy adults. In both humans and vaccine-tested animals, neutralizing titers elicited by this subtype A DS-Cav1 immunogen were ~ 2- to 3-fold higher against the homologous subtype A virus than against the heterologous subtype B virus.
methodsTo understand the molecular basis for this subtype difference, we introduced DS-Cav1 mutations into RSV strain B18537 F, determined the trimeric crystal structure, and carried out immunogenicity studies.
resultsThe B18537 DS-Cav1 F structure at 2-Å resolution afforded a precise delineation of prefusion F characteristics, including those of antigenic site Ø, a key trimer-apex site. Structural comparison with the subtype A prefusion F indicated 11% of surface residues to be different, with an alpha-carbon root-mean-square deviation (RMSD) of 1.2 Å; antigenic site Ø, however, differed in 23% of its surface residues and had an alpha-carbon RMSD of 2.2 Å. Immunization of vaccine-tested animals with DS-Cav1-stabilized B18537 F induced neutralizing responses ~100-fold higher than with postfusion B18537 F. Notably, elicited responses neutralized RSV subtypes A and B at similar levels and were directed towards both conserved equatorial and diverse apical regions.
conclusionWe propose that structural differences in apical and equatorial sites-coupled to differently focused immune responses-provide a molecular explanation for observed differences in elicited subtype A and B neutralizing responses.
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