Evidence map›Paper›PMID 33826885›Full record

ArticleCell reports2021

Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.

Ronald Derking, Joel D Allen, Christopher A Cottrell, Kwinten Sliepen, Gemma E Seabright, Wen-Hsin Lee, Yoann Aldon, Kimmo Rantalainen, Aleksandar Antanasijevic, Jeffrey Copps and 15 more

Abstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing 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

47 citing papers in PubMed.

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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

25 authors.

Ronald DerkingDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kwinten SliepenDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Gemma E SeabrightSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Wen-Hsin LeeDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Yoann AldonDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Kimmo RantalainenDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Aleksandar AntanasijevicDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jeffrey CoppsDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Anila YasmeenDepartment of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Albert CupoDepartment of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Victor M Cruz PortilloDepartment of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Meliawati PonimanDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Niki BolDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Patricia van der WoudeDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Steven W de TaeyeDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
Tom L G M van den KerkhofDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
P J KlasseDepartment of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Marit J van GilsDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands.
John P MooreDepartment of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Development, IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK. Electronic address: max.crispin@soton.ac.uk.
Rogier W SandersDepartment of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Electronic address: r.w.sanders@amsterdamumc.nl.

Funding

Identification of neutralizing epitopes on SARS-CoV-2 spike for design of vaccines and small-molecule antiviralsUM1AI144462 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2019 to 2025
$201.6M
Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BAROUCH, DAN H. · 2012 to 2018
$131.5M
Structural studies of native-like SOSIP trimersP01AI110657 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 2015 to 2024
$35.4M
Broadening autologous Tier 2 anti-HIV neutralizing antibodiesF31AI131873 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI COTTRELL, CHRISTOPHER ANDREW · 2017 to 2020
$95k
NIAID NIH HHS F31 AI131873NIAID NIH HHS P01 AI110657NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1 AI144462
6 · The paper itself

Abstract

Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.

Indexed as

Protein MultimerizationAnimalsCHO CellsCricetulusCryoelectron Microscopyenv Gene Products, Human Immunodeficiency VirusGlycosylationHEK293 CellsHexosyltransferasesHIV-1HumansMembrane ProteinsModels, MolecularPolysaccharidesSolubilitydolichyl-diphosphooligosaccharide - protein glycotransferaseenv Gene Products, Human Immunodeficiency VirusHexosyltransferasesMembrane ProteinsPolysaccharidescryo-EMglycan occupancyHIV-1 vaccine researchmass spectrometry

Identifiers

PMID33826885
PMCPMC8804554

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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.