Evidence map›Paper›PMID 36633409›Full record

ArticleJournal of virology2023

Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield.

Daniel Wrapp, Zekun Mu, Bhishem Thakur, Katarzyna Janowska, Oluwatobi Ajayi, Maggie Barr, Robert Parks, Katayoun Mansouri, Robert J Edwards, Beatrice H Hahn and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 19 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

13 authors at 3 institutions in 1 country.

Daniel WrappDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.ORCID 0000-0002-0538-9647
Zekun MuDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Bhishem ThakurDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Katarzyna JanowskaDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Oluwatobi AjayiDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Maggie BarrDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Robert ParksDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Katayoun MansouriDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Robert J EdwardsDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Beatrice H HahnDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Priyamvada AcharyaDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Kevin O SaundersDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Barton F HaynesDuke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Duke Medical Center · USDuke University · USUniversity of Pennsylvania · US

Funding

Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogensR37AI150590 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Beatrice H Hahn · 2019 to 2026
$6.9M
Natural SIV Reservoirs and Human Zoonotic RiskR01AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2001 to 2022
$6.1M
Natural SIV Reservoirs and Human Zoonotic RiskR37AI050529 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HAHN, BEATRICE H · 2008 to 2017
$5.7M
NIAID NIH HHS P01 AI131251NIAID NIH HHS R01 AI050529NIAID NIH HHS R37 AI050529NIAID NIH HHS R37 AI150590NIAID NIH HHS T32 AI007392NIAID NIH HHS UM1 AI144371
6 · The paper itself

Abstract

The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expression due to their inherent metastability, making biochemical and immunological experiments impractical or impossible. Here, we report a novel proline stabilization strategy to facilitate the production of prefusion Env trimers. This approach, termed "2P," works synergistically with previously described SOSIP mutations and dramatically increases the yield of recombinantly expressed Env ectodomains without altering the antigenic or conformational properties of near-native Env. We determined that the 2P mutations function by enhancing the durability of the prefusion conformation and that this stabilization strategy is broadly applicable to evolutionarily and antigenically diverse Env constructs. These findings provide a new Env stabilization platform to facilitate biochemical research and expand the number of Env variants that can be developed as future HIV-1 vaccine candidates.

Indexed as

env Gene Products, Human Immunodeficiency VirusGlycoproteinsHIV-1HIV InfectionsHumansMolecular ConformationProtein EngineeringProtein MultimerizationRecombinant Proteinsenv Gene Products, Human Immunodeficiency VirusGlycoproteinsRecombinant Proteinscryo-EMHIV-1immunogen designprefusionproline stabilization

Identifiers

PMID36633409
PMCPMC9888283
OpenAlexW4315752534

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.