Evidence map›Paper›PMID 29653575›Full record

ArticleJournal of nanobiotechnology2018

Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide.

Jens Schumacher, Tijana Bacic, René Staritzbichler, Matin Daneschdar, Thorsten Klamp, Philipp Arnold, Sabrina Jägle, Özlem Türeci, Jürgen Markl, Ugur Sahin

Open access · goldAbstract read
In one paragraph

Article in Journal of nanobiotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
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

18 citing papers in PubMed, 33 citations in OpenAlex.

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  14. Vaccines · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Jens SchumacherBiopharmaceutical New Technologies (BioNTech) Protein Therapeutics Corporation, An der Goldgrube 12, 55131, Mainz, Germany.
Tijana BacicBiopharmaceutical New Technologies (BioNTech) Protein Therapeutics Corporation, An der Goldgrube 12, 55131, Mainz, Germany.
René StaritzbichlerTRON Translational Oncology, University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
Matin DaneschdarDepartment of Internal Medicine III, Translational and Experimental Oncology, University Medical Center of Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany.
Thorsten KlampBiopharmaceutical New Technologies (BioNTech) Protein Therapeutics Corporation, An der Goldgrube 12, 55131, Mainz, Germany.
Philipp ArnoldInstitute of Zoology, Johannes Gutenberg University, Johannes-von-Müller-Weg 6, 55128, Mainz, Germany.
Sabrina JägleBiopharmaceutical New Technologies (BioNTech) Protein Therapeutics Corporation, An der Goldgrube 12, 55131, Mainz, Germany.
Özlem TüreciGanymed Pharmaceuticals AG, An der Goldgrube 12, 55131, Mainz, Germany.
Jürgen MarklInstitute of Zoology, Johannes Gutenberg University, Johannes-von-Müller-Weg 6, 55128, Mainz, Germany.
Ugur SahinBiopharmaceutical New Technologies (BioNTech) Protein Therapeutics Corporation, An der Goldgrube 12, 55131, Mainz, Germany. sahin@uni-mainz.de.
Johannes Gutenberg University Mainz · DETranslationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz · DE

Funding

Bundesministerium für Bildung und Forschung (DE) FKZ 131A016A
6 · The paper itself

Abstract

backgroundVirus-like-particles (VLPs) are attractive nanoparticulate scaffolds for broad applications in material/biological sciences and medicine. Prior their functionalization, specific adaptations have to be carried out. These adjustments frequently lead to disordered particles, but the particle integrity is an essential factor for the VLP suitability. Therefore, major requirements for particle stabilization exist. The objective of this study was to evaluate novel stabilizing elements for functionalized chimeric hepatitis B virus core antigen virus-like particles (HBcAg-VLP), with beneficial characteristics for vaccine development, imaging or delivery.

resultsThe effects of a carboxy-terminal polyhistidine-peptide and an intradimer disulfide-bridge on the stability of preclinically approved chimeric HBcAg-VLPs were assessed. We purified recombinant chimeric HBcAg-VLPs bearing different modified C-termini and compared their physical and chemical particle stability by quantitative protein-biochemical and biophysical techniques. We observed lower chemical resistance of T = 3- compared to T = 4-VLP (triangulation number) capsids and profound impairment of accessibility of hexahistidine-peptides in assembled VLPs. Histidines attached to the C-terminus were associated with superior mechanical and/or chemical particle stability depending on the number of histidine moieties. A molecular modeling approach based on cryo-electron microscopy and biolayer interferometry revealed the underlying structural mechanism for the strengthening of the integrity of VLPs. Interactions triggering capsid stabilization occur on a highly conserved residue on the basis of HBcAg-monomers as well as on hexahistidine-peptides of adjacent monomers. This new stabilization mechanism appears to mimic an evolutionary conserved stabilization concept for hepadnavirus core proteins.

conclusionsThese findings establish the genetically simply transferable C-terminal polyhistidine-peptide as a general stabilizing element for chimeric HBcAg-VLPs to increase their suitability.

Indexed as

Hepatitis B Core AntigensHistidineModels, MolecularOligopeptidesQuality ControlRecombinant ProteinsStress, PhysiologicalVirionHepatitis B Core AntigensHis-His-His-His-His-HisHistidineOligopeptidesRecombinant ProteinsBioengineeringBionanoparticlesCapsid and particle stabilityChimeric VLPComputational biologyHepatitis B virusMolecular mechanismStructural biologyVaccineVirus-like-particles (VLP)

Identifiers

PMID29653575
PMCPMC5897928
OpenAlexW2797084200

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.