Evidence map›Paper›PMID 41779867›Full record

ArticleScience translational medicine2026

Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice.

Annie Dosey, Bernadeta Dadonaite, Rebecca A Gillespie, Elizabeth M Leaf, Matthew J Vukovich, Jackson McGowan, Emily Grey, Hiromi Muramatsu, Rachel H J Jun, Norbert Pardi and 3 more

Abstract read
In one paragraph

Article in Science translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Annie DoseyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-6858-4725
Bernadeta DadonaiteBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.ORCID 0000-0003-0908-6982
Rebecca A GillespieVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-5741-3699
Elizabeth M LeafDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-5354-6010
Matthew J VukovichVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-7110-9623
Jackson McGowanDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0009-0002-6418-3371
Emily GreyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0003-1153-7471
Hiromi MuramatsuDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-1544-1493
Rachel H J JunAcuitas Therapeutics, Vancouver, British Columbia V6T 1Z3, Canada.ORCID 0009-0008-9733-4715
Norbert PardiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-1008-6242
Masaru KanekiyoVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-5767-1532
Jesse D BloomBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.ORCID 0000-0003-1267-3408
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-2978-4692

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00015 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HENSLEY, SCOTT · 2021 to 2025
$50.7M
Project 5: mRNA and mRNA-launched nanoparticle vaccinesU19AI181881 · NIAID · UNIVERSITY OF WASHINGTON · PI BLOOM, JESSE D · 2024 to 2024
$41.1M
Structure-based design of broadly protective coronavirus vaccinesP01AI167966 · NIAID · UNIVERSITY OF WASHINGTON · PI BALI PULENDRAN · 2022 to 2026
$15.3M
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteinsR01AI141707 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2018 to 2022
$2.1M
NIAID NIH HHS 75N93021C00015NIAID NIH HHS P01 AI167966NIAID NIH HHS R01 AI141707NIAID NIH HHS U19 AI181881NIH HHS 75N93021C00015
6 · The paper itself

Abstract

Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA-lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.

Indexed as

Antibodies, NeutralizingAntibody FormationHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesAnimalsAntibodies, ViralEpitope MappingFemaleHumansInfluenza A Virus, H5N1 SubtypeMiceMice, Inbred BALB CMutationProtein StabilityAntibodies, NeutralizingAntibodies, ViralHemagglutinin Glycoproteins, Influenza VirusInfluenza Vaccines

Identifiers

PMID41779867
PMCPMC13108606

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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.