Evidence map›Paper›PMID 35228534›Full record

ArticleNPJ vaccines2022

High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.

Iván Del Moral-Sánchez, Rebecca A Russell, Edith E Schermer, Christopher A Cottrell, Joel D Allen, Alba Torrents de la Peña, Celia C LaBranche, Sanjeev Kumar, Max Crispin, Andrew B Ward and 4 more

Open access · goldAbstract read
In one paragraph

Article in NPJ vaccines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.8field-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

25 citing papers in PubMed, 26 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

14 authors at 6 institutions in 4 countries.

Iván Del Moral-SánchezDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Rebecca A RussellThe Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6517-6483
Edith E SchermerDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Christopher A CottrellDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-3364-3083
Joel D AllenSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0003-2547-968X
Alba Torrents de la PeñaDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Celia C LaBrancheDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-6653-6655
Sanjeev KumarDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0000-0002-8181-3999
Max CrispinSchool of Biological Sciences, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0002-1072-2694
Andrew B WardDepartment of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7153-3769
David C MontefioriDepartment of Surgery, Duke University School of Medicine, Durham, NC, USA.
Quentin J SattentauThe Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-7170-1937
Kwinten SliepenDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.ORCID http://orcid.org/0000-0003-1414-0648
Rogier W SandersDepartment of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. r.w.sanders@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-2324-8573
Amsterdam University Medical Centers · NLScripps Research Institute · USDuke University · USUniversity of Oxford · GBUniversity of Southampton · GBCornell University · 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
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) OPP1111923 and OPP1132237Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) P01AI110657Medical Research Council G0000635NIAID NIH HHS P01 AI110657
6 · The paper itself

Abstract

Soluble HIV-1 envelope glycoprotein (Env) immunogens are a prime constituent of candidate vaccines designed to induce broadly neutralizing antibodies. Several lines of evidence suggest that enhancing Env immunogen thermostability can improve neutralizing antibody (NAb) responses. Here, we generated BG505 SOSIP.v9 trimers, which displayed virtually no reactivity with non-neutralizing antibodies and showed increased global and epitope thermostability, compared to previous BG505 SOSIP versions. Chemical crosslinking of BG505 SOSIP.v9 further increased the melting temperature to 91.3 °C, which is almost 25 °C higher than that of the prototype SOSIP.664 trimer. Next, we compared the immunogenicity of a palette of BG505-based SOSIP trimers with a gradient of thermostabilities in rabbits. We also included SOSIP.v9 proteins in which a strain-specific immunodominant epitope was masked by glycans to redirect the NAb response to other subdominant epitopes. We found that increased trimer thermostability correlated with increased potency and consistency of the autologous NAb response. Furthermore, glycan masking steered the NAb response to subdominant epitopes without decreasing the potency of the autologous NAb response. In summary, SOSIP.v9 trimers and their glycan masked versions represent an improved platform for HIV-1 Env based vaccination strategies.

Identifiers

PMID35228534
PMCPMC8885667
OpenAlexW4214674548

What OpenQuestion holds

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LicenceCC BY
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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.