Evidence map›Paper›PMID 37292995›Full record

ArticlebioRxiv : the preprint server for biology2023

Antigen spacing on protein nanoparticles influences antibody responses to vaccination.

Daniel Ellis, Annie Dosey, Seyhan Boyoglu-Barnum, Young-Jun Park, Rebecca Gillespie, Hubza Syeda, Yaroslav Tsybovsky, Michael Murphy, Deleah Pettie, Nick Matheson and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Daniel EllisInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Annie DoseyInstitute 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.
Young-Jun ParkDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Rebecca GillespieVaccine 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.
Yaroslav TsybovskyVaccine Research Center Electron Microscopy Unit, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA.
Michael MurphyInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Deleah PettieInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Nick MathesonInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Sidney ChanInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
George UedaInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jorge A FallasInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Lauren CarterInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Barney S GrahamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
David VeeslerDepartment of Biochemistry, 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 KingInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.

Funding

Structure-based design of broadly protective coronavirus vaccinesP01AI167966 · NIAID · UNIVERSITY OF WASHINGTON · PI BALI PULENDRAN · 2022 to 2026
$15.3M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENIAID NIH HHS P01 AI167966
6 · The paper itself

Abstract

Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship between immunogen structure and immunogenicity is limited. Here we use computational protein design to generate a self-assembling nanoparticle vaccine platform based on the head domain of influenza hemagglutinin (HA) that enables precise control of antigen conformation, flexibility, and spacing on the nanoparticle exterior. Domain-based HA head antigens were presented either as monomers or in a native-like closed trimeric conformation that prevents exposure of trimer interface epitopes. These antigens were connected to the underlying nanoparticle by a rigid linker that was modularly extended to precisely control antigen spacing. We found that nanoparticle immunogens with decreased spacing between closed trimeric head antigens elicited antibodies with improved hemagglutination inhibition (HAI) and neutralization potency as well as binding breadth across diverse HAs within a subtype. Our "trihead" nanoparticle immunogen platform thus enables new insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used to generate next-generation vaccines against influenza and other viruses.

Identifiers

PMID37292995
PMCPMC10245855

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.