ArticleJournal of molecular biology2011
Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 111 citations in OpenAlex.
- Deep learning-enabled scaffolding of spatial arrays of PfCSP epitopes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Accurate single-domain scaffolding of three nonoverlapping protein epitopes using deep learning.Nature chemical biology · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Epitope-focused vaccine immunogens design using tailored horseshoe-shaped scaffold.Journal of nanobiotechnology · 2025Article
- Rational structure-guided design of a blood stage malaria vaccine immunogen presenting a single epitope from PfRH5.EMBO molecular medicine · 2024Article
- Bringing immunofocusing into focus.NPJ vaccines · 2024Review
- Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.Nature communications · 2023Article
- Structural basis for respiratory syncytial virus and human metapneumovirus neutralization.Current opinion in virology · 2023Review
- Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVFrontiers in immunology · 2023Article
- Adaptation-proof SARS-CoV-2 vaccine design.Advanced functional materials · 2022Article
- Backbone and side-chain resonance assignments of the NISTmAb-scFv and antigen-binding study.Biomolecular NMR assignments · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
- Epitope-focused immunogen design based on the ebolavirus glycoprotein HR2-MPER region.PLoS pathogens · 2022Article
- Toward rational vaccine engineering.Advanced drug delivery reviews · 2022Review
- Review
- An epitope-specific chemically defined nanoparticle vaccine for respiratory syncytial virus.NPJ vaccines · 2021Article
- Vaccine development lessons between HIV and COVID-19.The Lancet. Infectious diseases · 2021Article
- Modeling Immunity with Rosetta: Methods for Antibody and Antigen Design.Biochemistry · 2021Review
- Potential neutralizing antibodies discovered for novel corona virus using machine learning.Scientific reports · 2021Article
- De novo protein design enables the precise induction of RSV-neutralizing antibodies.Science (New York, N.Y.) · 2020Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.