Evidence map›Paper›PMID 35288548›Full record

ArticleNature communications2022

Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins.

Ching-Lin Hsieh, Scott A Rush, Concepcion Palomo, Chia-Wei Chou, Whitney Pickens, Vicente Más, Jason S McLellan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

61 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Twenty-five years of human metapneumovirus research.Clinical microbiology reviews · 2026
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1 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 2 countries.

Ching-Lin HsiehDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0002-3665-5717
Scott A RushDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0002-9601-5068
Concepcion PalomoCentro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Chia-Wei ChouDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Whitney PickensDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.ORCID 0000-0001-6100-8231
Vicente MásCentro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Jason S McLellanDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. jmclellan@austin.utexas.edu.ORCID 0000-0003-3991-542X
The University of Texas at Austin · USInstituto de Salud Carlos III · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies.

Indexed as

MetapneumovirusAnimalsAntibodies, NeutralizingAntibodies, ViralHumansImmunizationMiceViral Fusion ProteinsAntibodies, NeutralizingAntibodies, ViralViral Fusion Proteins

Identifiers

PMID35288548
PMCPMC8921277
OpenAlexW4220994000

What OpenQuestion holds

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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.