ArticleACS infectious diseases2020
Structure-Guided Molecular Grafting of a Complex Broadly Neutralizing Viral Epitope.
Article in ACS infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses.Nature microbiology · 2025Article
- Structure-based Design of Chimeric Influenza Hemagglutinins to Elicit Cross-group Immunity.bioRxiv : the preprint server for biology · 2025Article
- Review
- Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation.ACS infectious diseases · 2024Article
- Antigen spacing on protein nanoparticles influences antibody responses to vaccination.Cell reports · 2023Article
- Heterologous sarbecovirus receptor binding domains as scaffolds for SARS-CoV-2 receptor binding motif presentation.bioRxiv : the preprint server for biology · 2023Article
- Antigen spacing on protein nanoparticles influences antibody responses to vaccination.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens.Cell reports · 2023Article
- An epitope-enriched immunogen expands responses to a conserved viral site.Cell reports · 2022Article
- Past, present, and future of Lyme disease vaccines: antigen engineering approaches and mechanistic insights.Expert review of vaccines · 2022Review
- Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus.Immunity · 2022Article
- Toward rational vaccine engineering.Advanced drug delivery reviews · 2022Review
- Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting.Cell reports · 2022Article
- Protein engineering strategies for rational immunogen design.NPJ vaccines · 2021Review
- Antibody Focusing to Conserved Sites of Vulnerability: The Immunological Pathways for 'Universal' Influenza Vaccines.Vaccines · 2021Review
- Altering the Immunogenicity of Hemagglutinin Immunogens by Hyperglycosylation and Disulfide Stabilization.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a "universal" influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These "resurfaced" HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological and single germinal center B cell analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can augment the quality of elicited RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.
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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.