Evidence map›Paper›PMID 28827559›Full record

ArticleScientific reports2017

Selection of nanobodies with broad neutralizing potential against primary HIV-1 strains using soluble subtype C gp140 envelope trimers.

Kathrin Koch, Sarah Kalusche, Jonathan L Torres, Robyn L Stanfield, Welbeck Danquah, Kamal Khazanehdari, Hagen von Briesen, Eric R Geertsma, Ian A Wilson, Ulrich Wernery and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

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  19. An update on antiviral antibody-based biopharmaceuticals.International immunopharmacology · 2020
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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 6 institutions in 3 countries.

Kathrin KochGeorg-Speyer-Haus, Paul-Ehrlich-Str, 42-44, 60596, Frankfurt, Germany.
Sarah KaluscheGeorg-Speyer-Haus, Paul-Ehrlich-Str, 42-44, 60596, Frankfurt, Germany.
Jonathan L TorresDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
Robyn L StanfieldDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
Welbeck DanquahInstitute of Immunology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Kamal KhazanehdariCentral Veterinary Research Laboratory, Dubai, United Arab Emirates.
Hagen von BriesenFraunhofer Institute for Biomedical Engineering, 66280, Sulzbach, Germany.
Eric R GeertsmaInstitute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany.ORCID 0000-0002-2789-5444
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.ORCID 0000-0002-6469-2419
Ulrich WerneryCentral Veterinary Research Laboratory, Dubai, United Arab Emirates.
Friedrich Koch-NolteInstitute of Immunology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
Andrew B WardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, 92037, USA.
Ursula DietrichGeorg-Speyer-Haus, Paul-Ehrlich-Str, 42-44, 60596, Frankfurt, Germany. ursula.dietrich@gsh.uni-frankfurt.de.
Scripps Research Institute · USGeorg Speyer Haus · DECentral Veterinary Research Laboratory · AEUniversität Hamburg · DEFraunhofer Institute for Biomedical Engineering · DEGoethe University Frankfurt · DE

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI GODZIK, ADAM · 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
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6M
Structural Biology of HIV-1 Neutralizing Antibody Targets for Vaccine DesignR01AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2009 to 2013
$3.2M
Structure and dynamics of native HIV-1 envelope trimersR56AI084817 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2015 to 2015
$593k
NIAID NIH HHS P01 AI110657NIAID NIH HHS R01 AI084817NIAID NIH HHS R56 AI084817NIAID NIH HHS UM1 AI100663NIGMS NIH HHS P41 GM103393
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bnAbs) against HIV-1 protect from infection and reduce viral load upon therapeutic applications. However no vaccine was able so far to induce bnAbs demanding their expensive biotechnological production. For clinical applications, nanobodies (VHH) derived from heavy chain only antibodies from Camelidae, may be better suited due to their small size, high solubility/stability and extensive homology to human VH3 genes. Here we selected broadly neutralizing nanobodies by phage display after immunization of dromedaries with different soluble trimeric envelope proteins derived from HIV-1 subtype C. We identified 25 distinct VHH families binding trimeric Env, of which 6 neutralized heterologous primary isolates of various HIV-1 subtypes in a standardized in vitro neutralization assay. The complementary neutralization pattern of two selected VHHs in combination covers 19 out of 21 HIV-1 strains from a standardized panel of epidemiologically relevant HIV-1 subtypes. The CD4 binding site was preferentially targeted by the broadly neutralizing VHHs as determined by competition ELISAs and 3D models of VHH-Env complexes derived from negative stain electron microscopy. The nanobodies identified here are excellent candidates for further preclinical/clinical development for prophylactic and therapeutic applications due to their potency and their complementary neutralization patterns covering the majority of epidemiologically relevant HIV-1 subtypes.

Indexed as

AnimalsAntibodies, NeutralizingCamelusCell Surface Display Techniquesenv Gene Products, Human Immunodeficiency VirusGenotypeHIV-1HIV AntibodiesHIV InfectionsHumansProtein BindingProtein ConformationSingle-Domain AntibodiesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency Virusgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesSingle-Domain Antibodies

Identifiers

PMID28827559
PMCPMC5566552
OpenAlexW2742379168

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.