Evidence map›Paper›PMID 28878072›Full record

ArticleJournal of virology2017

High-Throughput Protein Engineering Improves the Antigenicity and Stability of Soluble HIV-1 Envelope Glycoprotein SOSIP Trimers.

Jonathan T Sullivan, Chidananda Sulli, Alberto Nilo, Anila Yasmeen, Gabriel Ozorowski, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore, Benjamin J Doranz

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Protein Stability: Enhancement and Measurement.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  7. Article
  8. Article
  9. Article
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  13. Article
  14. Innovations in HIV-1 Vaccine Design.Clinical therapeutics · 2020
    Review
  15. Article
  16. Article
  17. Article
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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 3 institutions in 2 countries.

Jonathan T SullivanIntegral Molecular, Philadelphia, Pennsylvania, USA.
Chidananda SulliIntegral Molecular, Philadelphia, Pennsylvania, USA.
Alberto NiloDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA.
Anila YasmeenDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA.
Gabriel OzorowskiDepartment of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California, USA.
Rogier W SandersDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA.
Andrew B WardDepartment of Integrative Structural and Computational Biology, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, California, USA.
P J KlasseDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA.
John P MooreDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA jpm2003@med.cornell.edu bdoranz@integralmolecular.com.
Benjamin J DoranzIntegral Molecular, Philadelphia, Pennsylvania, USA jpm2003@med.cornell.edu bdoranz@integralmolecular.com.
Cornell University · USIntegral Molecular (United States) · USInternational AIDS Vaccine Initiative · US

Funding

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
Engineering Stable, Soluble, and Trimeric HIV gp140 by Paired Cys ScanningR43AI102626 · NIAID · INTEGRAL MOLECULAR · PI DORANZ, BENJAMIN J · 2012 to 2013
$546k
NIAID NIH HHS P01 AI110657NIAID NIH HHS R37 AI036082NIAID NIH HHS R43 AI102626
6 · The paper itself

Abstract

Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140. The parental protein target, the clade B strain B41 SOSIP.664 gp140, does not bind the broadly neutralizing antibody PGT151 and so was used here to identify improved variants that also provide insight into the structural basis for Env antigenicity. Each of the 852 mutants was expressed in human cells and screened for antigenicity using four different monoclonal antibodies (MAbs), including PGT151. We identified 29 trimer variants with antigenic improvements derived from each of the three mutagenesis strategies. We selected four variants (Q203F, T538F, I548F, and M629P) for more comprehensive biochemical, structural, and antigenicity analyses. The T538F substitution had the most beneficial effect overall, including restoration of the PGT151 epitope. The improved B41 SOSIP.664 trimer variants identified here may be useful for vaccine and structural studies.

Indexed as

Amino Acid SubstitutionMutagenesisMutation, MissenseAIDS VaccinesAntibodies, Monoclonal, Murine-DerivedAntibodies, NeutralizingHEK293 CellsHIV-1HIV AntibodiesHIV Envelope Protein gp160HumansAIDS VaccinesAntibodies, Monoclonal, Murine-DerivedAntibodies, NeutralizingHIV AntibodiesHIV Envelope Protein gp160gp140human immunodeficiency virusimmunizationprotein engineeringshotgun mutagenesistrimer

Identifiers

PMID28878072
PMCPMC5660478
OpenAlexW2752978677

What OpenQuestion holds

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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.