Evidence map›Paper›PMID 30487280›Full record

ArticleJournal of virology2019

Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.

Rajesh P Ringe, Pavel Pugach, Christopher A Cottrell, Celia C LaBranche, Gemma E Seabright, Thomas J Ketas, Gabriel Ozorowski, Sonu Kumar, Anna Schorcht, Marit J van Gils and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 86 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

17 authors at 5 institutions in 3 countries.

Rajesh P RingeDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Pavel PugachDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Christopher A CottrellDepartment of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.
Celia C LaBrancheDepartment of Surgery, Duke University Medical Center, Durham, North Carolina, USA.ORCID 0000-0002-6653-6655
Gemma E SeabrightBiological Sciences & The Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
Thomas J KetasDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.ORCID 0000-0002-9695-8138
Sonu KumarDepartment of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.
Anna SchorchtDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Marit J van GilsDepartment of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Max CrispinBiological Sciences & The Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
David C MontefioriDepartment of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA.
Rogier W SandersDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA.
P J KlasseDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA pek2003@med.cornell.edu jpm2003@med.cornell.edu.
John P MooreDepartment of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, USA pek2003@med.cornell.edu jpm2003@med.cornell.edu.
Cornell University · USScripps Research Institute · USAmsterdam UMC Location University of Amsterdam · NLDuke Medical Center · USUniversity of Southampton · GB

Funding

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
NEUTRALIZATION OF PRIMARY HIV1 VIRUSESR37AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI MOORE, JOHN P · 1998 to 2017
$7.0M
Neutralization of Primate Immunodeficiency VirusesR01AI036082 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI JOHN P MOORE · 1994 to 2026
$4.3M
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 R01 AI036082NIAID NIH HHS R37 AI036082NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals. The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces. For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241. Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241. We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites. The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site. We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer. Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out. In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.

Indexed as

AIDS VaccinesAnimalsAntibodies, NeutralizingAntibody FormationAntigens, Viralenv Gene Products, Human Immunodeficiency VirusEpitopesFemaleGlycoproteinsHIV-1HIV AntibodiesHIV InfectionsImmunizationPolysaccharidesRabbitsAIDS VaccinesAntibodies, NeutralizingAntigens, Viralenv Gene Products, Human Immunodeficiency VirusEpitopesGlycoproteinsHIV AntibodiesPolysaccharidesantibodiesEnv trimerepitopeglycan holeHIV-1immunizationneutralizationSOSIP

Identifiers

PMID30487280
PMCPMC6363999
OpenAlexW2903361904

What OpenQuestion holds

Textmetadata
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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.