Evidence map›Paper›PMID 27793398›Full record

ArticleImmunobiology2017

Novel expression of a functional trimeric fragment of human SP-A with efficacy in neutralisation of RSV.

Alastair Watson, Nina Kronqvist, C Mirella Spalluto, Mark Griffiths, Karl J Staples, Tom Wilkinson, Uffe Holmskov, Grith L Sorensen, Anna Rising, Jan Johansson and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Immunobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

22 citing papers in PubMed, 27 citations in OpenAlex.

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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

12 authors at 5 institutions in 3 countries.

Alastair WatsonClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
Nina KronqvistDivision for Neurogeriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 57 Huddinge, Sweden.
C Mirella SpallutoClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
Mark GriffithsLeukocyte Biology, Imperial College London, Royal Brompton Campus, London SW3 6NP, United Kingdom.
Karl J StaplesClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom.
Tom WilkinsonClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom; Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom.
Uffe HolmskovInstitute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Grith L SorensenInstitute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Anna RisingDivision for Neurogeriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 57 Huddinge, Sweden; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, 750 07 Uppsala, Sweden.
Jan JohanssonDivision for Neurogeriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 57 Huddinge, Sweden; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Box 7011, 750 07 Uppsala, Sweden.
Jens MadsenClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom; Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, United Kingdom.
Howard ClarkClinical & Experimental Sciences Academic Unit, Southampton General Hospital, University of Southampton, Southampton, United Kingdom; Division for Neurogeriatrics, Center for Alzheimer Research, Department of NVS, Karolinska Institutet, 141 57 Huddinge, Sweden; Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom. Electronic address: H.W.Clark@soton.ac.uk.
University of Southampton · GBKarolinska Institutet · SESouthampton General Hospital · GBUniversity of Southern Denmark · DKRoyal Brompton Hospital · GB

Funding

Medical Research Council
6 · The paper itself

Abstract

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalisation of infants in developed countries. Surfactant protein A (SP-A) is an important innate immune molecule, localized in pulmonary surfactant. SP-A binds to carbohydrates on the surface of pathogens in a calcium-dependent manner to enable neutralisation, agglutination and clearance of pathogens including RSV. SP-A forms trimeric units and further oligomerises through interactions between its N-terminal domains. Whilst a recombinant trimeric fragment of the closely related molecule (surfactant protein D) has been shown to retain many of the native protein's functions, the importance of the SP-A oligomeric structure in its interaction with RSV has not been determined. The aim of this study was to produce a functional trimeric recombinant fragment of human (rfh)SP-A, which lacks the N-terminal domain (and the capacity to oligomerise) and test its ability to neutralise RSV in an in vitro model of human bronchial epithelial infection. We used a novel expression tag derived from spider silk proteins ('NT') to produce rfhSP-A in Escherichia coli, which we found to be trimeric and to bind to mannan in a calcium-dependent manner. Trimeric rfhSP-A reduced infection levels of human bronchial epithelial (AALEB) cells by RSV by up to a mean (±SD) of 96.4 (±1.9) % at 5μg/ml, which was significantly more effective than dimeric rfhSP-A (34.3 (±20.5) %) (p<0.0001). Comparatively, native human SP-A reduced RSV infection by up to 38.5 (±28.4) %. For the first time we report the development of a functional trimeric rfhSP-A molecule which is highly efficacious in neutralising RSV, despite lacking the N-terminal domain and capacity to oligomerise.

Indexed as

Gene ExpressionProtein MultimerizationCarbohydrate MetabolismCarbohydratesCells, CulturedHost-Pathogen InteractionsHumansProtein BindingPulmonary Surfactant-Associated Protein ARecombinant Fusion ProteinsRespiratory MucosaRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsCarbohydratesPulmonary Surfactant-Associated Protein ARecombinant Fusion ProteinsCollectinInnate immunityNeutralisationNT domainRecombinant trimeric fragmentRespiratory syncytial virusSurfactant protein A

Identifiers

PMID27793398
PMCPMC5152705
OpenAlexW2539142691

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.