Evidence map›Paper›PMID 38096052›Full record

ArticleCell reports2023

Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.

Annie Dosey, Daniel Ellis, Seyhan Boyoglu-Barnum, Hubza Syeda, Mason Saunders, Michael J Watson, John C Kraft, Minh N Pham, Miklos Guttman, Kelly K Lee and 2 more

Abstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. Article
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  8. From sequence to scaffold: Computational design of protein nanoparticle vaccines from AlphaFold2-predicted building blocks.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Immunofocusing design of a fusion glycoprotein monomer vaccine for respiratory syncytial virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  10. Article
  11. Article
  12. Molecular divergence and convergence of mammalian antibody responses to the influenza virus hemagglutinin stem.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Annie DoseyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Daniel EllisDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Seyhan Boyoglu-BarnumVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hubza SyedaVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mason SaundersDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Michael J WatsonDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
John C KraftDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Minh N PhamDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Miklos GuttmanDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
Masaru KanekiyoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA. Electronic address: neilking@uw.edu.

Funding

Structure-based design of broadly protective coronavirus vaccinesP01AI167966 · NIAID · UNIVERSITY OF WASHINGTON · PI Neil King, David Veesler · 2022 to 2026
$15.3M
TRAINING IN MOLECULAR BIOPHYSICST32GM008268 · NIGMS · UNIVERSITY OF WASHINGTON · PI KOLLMAN, JUSTIN M, ZHENG, NING · 1988 to 2023
$8.6M
NIAID NIH HHS P01 AI167966NIGMS NIH HHS T32 GM008268
6 · The paper itself

Abstract

The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing techniques to enhance the functional breadth of vaccine-elicited immune responses against the HA RBD. We present a series of "trihead" nanoparticle immunogens that display native-like closed trimeric RBDs from the HAs of several H1N1 influenza viruses. The series includes hyperglycosylated and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the receptor-binding site periphery. Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicit higher hemagglutination inhibition (HAI) and neutralizing activity than the corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation. By contrast, mosaic nanoparticle display and antigen hypervariation do not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Our results yield important insights into antibody responses against the RBD and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.

Indexed as

Influenza A Virus, H1N1 SubtypeInfluenza, HumanInfluenza VaccinesOrthomyxoviridae InfectionsAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesHemagglutinin Glycoproteins, Influenza VirusHemagglutininsHumansAntibodies, NeutralizingAntibodies, ViralBroadly Neutralizing AntibodiesHemagglutinin Glycoproteins, Influenza VirusHemagglutininsInfluenza Vaccinesantigen designco-displayCP: ImmunologyEMPEMhemagglutininhyperglycosylationimmune focusinginfluenzananoparticlevaccine

Identifiers

PMID38096052
PMCPMC10801708

What OpenQuestion holds

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Registered trials

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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.