Evidence map›Paper›PMID 40661529›Full record

ArticlebioRxiv : the preprint server for biology2025

Design, Structure, and Immunogenicity of a Soluble Prefusion-stabilized EBV gB Antigen.

Ryan S McCool, Cory M Acreman, Abigail E Powell, Sofia I Picucci, Daniel J Stieh, Jeremy Huynh, Hannah Caruso, Soyoon Park, Jessica O'Rear, Jui-Lin Chen and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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.

Ryan S McCoolDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0001-8833-8847
Cory M AcremanDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0009-0004-8064-2245
Abigail E PowellVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0000-0001-6408-9495
Sofia I PicucciDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0009-0004-2173-3497
Daniel J StiehVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0009-0003-8523-1528
Jeremy HuynhVaccine Company, Inc., South San Francisco, California, 94080, USA.
Hannah CarusoVaccine Company, Inc., South San Francisco, California, 94080, USA.
Soyoon ParkVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0000-0002-7399-411X
Jessica O'RearVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0009-0008-6533-469X
Jui-Lin ChenVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0000-0002-7646-4907
Brad A PalanskiVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0000-0002-4049-4274
Patrick O ByrneDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0002-6462-8951
Madeline R SponholtzDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0002-0671-670X
Chia-Wei ChouDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0001-9618-338X
Jeongryeol KimDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0003-3506-5173
Julie E LedgerwoodVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0009-0000-7177-8993
Payton A-B WeidenbacherVaccine Company, Inc., South San Francisco, California, 94080, USA.ORCID 0000-0002-7692-0458
Jason S McLellanDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, 78712, USA.ORCID 0000-0003-3991-542X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epstein-Barr virus (EBV), the causative agent of mononucleosis, is linked to over 140,000 annual cancer-related deaths globally and increases the risk of multiple sclerosis by up to 32-fold. As a herpesvirus, EBV establishes lifelong infection, and over 90% of U.S. adults are EBV-seropositive. Despite its significant disease burden, no approved EBV vaccines or therapeutics exist. Among EBV envelope glycoproteins, the fusion protein (gB) is strictly required for epithelial and B cell infection. Using a combination of AlphaFold-guided modeling, rational design, and ThermoMPNN-informed optimization, we engineered a stabilized prefusion gB variant, D2C3. This construct incorporates two inter-protomeric disulfide bonds and three cavity-filling substitutions, resulting in a melting temperature of 54 °C. Cryo-EM analysis of this construct allowed us to determine the prefusion structure of EBV gB, providing insights into the structural transitions required to adopt the postfusion conformation. Murine immunizations and depletion studies with human sera suggested a trend toward improved functional immunogenicity of D2C3 compared to postfusion gB. Collectively, these studies define engineering principles to stabilize class III fusion proteins, provide reagents to interrogate the human antibody response to EBV gB, and lay a foundation for further studies to develop EBV gB-based vaccine candidates.

Identifiers

PMID40661529
PMCPMC12258704

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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.