ArticleProceedings of the National Academy of Sciences of the United States of America2010
Elicitation of structure-specific antibodies by epitope scaffolds.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
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Who cites it
180 citing papers in PubMed.
- Design of a novel proteome-derived scaffold presenting epitopes of Pseudomonas aeruginosa in native conformation.Scientific reports · 2026Article
- 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
- HIV Membrane-Proximal External Region Scaffolded Immunogen as Killed Whole-Cell Genome-Reduced Vaccines.Viruses · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Iterative immunogen optimization to focus immune responses on a conserved, subdominant viral epitope.bioRxiv : the preprint server for biology · 2025Article
- Manipulation of immunodominant variable epitopes of norovirus capsid protein elicited cross-blocking antibodies to different GII.4 variants despite the low potency of the polyclonal sera.Journal of virology · 2025Article
- Design of immunogens to present a tumor-specific cryptic epitope.Scientific reports · 2025Article
- Vaccination induces broadly neutralizing antibody precursors to HIV gp41.Nature immunology · 2024Article
- Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation.ACS infectious diseases · 2024Article
- Article
- Bringing immunofocusing into focus.NPJ vaccines · 2024Review
- Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.Nature communications · 2023Article
- Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility.Nature communications · 2023Article
- Mapping antibody footprints using binding profiles.Cell reports methods · 2023Article
- Heterologous sarbecovirus receptor binding domains as scaffolds for SARS-CoV-2 receptor binding motif presentation.bioRxiv : the preprint server for biology · 2023Article
- Adaptation-proof SARS-CoV-2 vaccine design.Advanced functional materials · 2022Article
- Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity.International journal of biological macromolecules · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
- Toward rational vaccine engineering.Advanced drug delivery reviews · 2022Review
120 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context has been a challenge for vaccine design. Here we demonstrate the elicitation of structure-specific antibodies against the HIV-1 gp41 epitope of the broadly neutralizing antibody 2F5. This conformationally flexible region of gp41 assumes mostly helical conformations but adopts a kinked, extended structure when bound by antibody 2F5. Computational techniques were employed to transplant the 2F5 epitope into select acceptor scaffolds. The resultant "2F5-epitope scaffolds" possessed nanomolar affinity for antibody 2F5 and a range of epitope flexibilities and antigenic specificities. Crystallographic characterization of the epitope scaffold with highest affinity and antigenic discrimination confirmed good to near perfect attainment of the target conformation for the gp41 molecular graft in free and 2F5-bound states, respectively. Animals immunized with 2F5-epitope scaffolds showed levels of graft-specific immune responses that correlated with graft flexibility (p < 0.04), while antibody responses against the graft-as dissected residue-by-residue with alanine substitutions-resembled more closely those of 2F5 than sera elicited with flexible or cyclized peptides, a resemblance heightened by heterologous prime-boost. Lastly, crystal structures of a gp41 peptide in complex with monoclonal antibodies elicited by the 2F5-epitope scaffolds revealed that the elicited antibodies induce gp41 to assume its 2F5-recognized shape. Epitope scaffolds thus provide a means to elicit antibodies that recognize a predetermined target shape and sequence, even if that shape is transient in nature, and a means by which to dissect factors influencing such elicitation.
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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.