Evidence map›Paper›PMID 23530120›Full record

ArticleThe Journal of experimental medicine2013

Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies.

Andrew T McGuire, Sam Hoot, Anita M Dreyer, Adriana Lippy, Andrew Stuart, Kristen W Cohen, Joseph Jardine, Sergey Menis, Johannes F Scheid, Anthony P West and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers.

0numbers the graph read from it
0cells of the map it votes in
255citing papers in PubMed
13.9field-weighted citation impact, top 1% 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

255 citing papers in PubMed, 319 citations in OpenAlex.

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195 more citing papers are in PubMed but not listed here.

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

12 authors at 6 institutions in 1 country.

Andrew T McGuireSeattle Biomedical Research Institute, Seattle, WA 98109, USA.
Sam Hoot
Anita M Dreyer
Adriana Lippy
Andrew Stuart
Kristen W Cohen
Joseph Jardine
Sergey Menis
Johannes F Scheid
Anthony P West
William R Schief
Leonidas Stamatatos
Center for Infectious Disease Research · USScripps Research Institute · USCalifornia Institute of Technology · USInternational AIDS Vaccine Initiative · USRockefeller University · USUniversity of Washington · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Grace C. John-Stewart · 1988 to 2026
$104.9M
Structure/function studies of immunogen recognition by anti-HIV antibody b12P01AI094419 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2011 to 2015
$10.6M
Interdisciplinary Tranining in Cancer ResearchT32CA080416 · NCI · UNIVERSITY OF WASHINGTON · PI STODDARD, BARRY L. · 1998 to 2023
$9.7M
Monitoring the development of anti-Env Abs during HIV infectionR01AI081625 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2010 to 2020
$5.8M
Vaccine Efficacy of Modified HIV EnvelopesR56AI047708 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2012 to 2012
$540k
NCI NIH HHS T32 CA080416NIAID NIH HHS P01AI081625NIAID NIH HHS P01 AI094419NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI081625NIAID NIH HHS R56 AI047708
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bnAbs) against HIV are believed to be a critical component of the protective responses elicited by an effective HIV vaccine. Neutralizing antibodies against the evolutionarily conserved CD4-binding site (CD4-BS) on the HIV envelope glycoprotein (Env) are capable of inhibiting infection of diverse HIV strains, and have been isolated from HIV-infected individuals. Despite the presence of anti-CD4-BS broadly neutralizing antibody (bnAb) epitopes on recombinant Env, Env immunization has so far failed to elicit such antibodies. Here, we show that Env immunogens fail to engage the germline-reverted forms of known bnAbs that target the CD4-BS. However, we found that the elimination of a conserved glycosylation site located in Loop D and two glycosylation sites located in variable region 5 of Env allows Env-binding to, and activation of, B cells expressing the germline-reverted BCRs of two potent broadly neutralizing antibodies, VRC01 and NIH45-46. Our results offer a possible explanation as to why Env immunogens have been ineffective in stimulating the production of such bNAbs. Importantly, they provide key information as to how such immunogens can be engineered to initiate the process of antibody-affinity maturation against one of the most conserved Env regions.

Indexed as

Protein EngineeringAIDS VaccinesAntibodies, NeutralizingCD4 AntigensCell Line, Tumorenv Gene Products, Human Immunodeficiency VirusGlycosylationHIV-1HIV AntibodiesHumansProtein Structure, SecondaryAIDS VaccinesAntibodies, NeutralizingCD4 Antigensenv Gene Products, Human Immunodeficiency VirusHIV Antibodies

Identifiers

PMID23530120
PMCPMC3620356
OpenAlexW2125878189

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.