Evidence map›Paper›PMID 23300456›Full record

ArticlePLoS pathogens2013

Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs.

Sam Hoot, Andrew T McGuire, Kristen W Cohen, Roland K Strong, Lars Hangartner, Florian Klein, Ron Diskin, Johannes F Scheid, D Noah Sather, Dennis R Burton and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 146 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 1 pooled it
9.8field-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

146 citing papers in PubMed, 1 synthesis or guideline pooled it, 190 citations in OpenAlex.

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

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

11 authors at 7 institutions in 1 country.

Sam HootSeattle Biomedical Research Institute, Seattle, WA, USA.
Andrew T McGuire
Kristen W Cohen
Roland K Strong
Lars Hangartner
Florian Klein
Ron Diskin
Johannes F Scheid
D Noah Sather
Dennis R Burton
Leonidas Stamatatos
Center for Infectious Disease Research · USRockefeller University · USCalifornia Institute of Technology · USFred Hutch Cancer Center · USInternational AIDS Vaccine Initiative · USScripps Research Institute · USUniversity of Washington · US

Funding

University of Washington/Fred Hutch Center for AIDS ResearchP30AI027757 · NIAID · UNIVERSITY OF WASHINGTON · PI Kenneth Sherr · 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
Monitoring the development of anti-Env Abs during HIV infectionR01AI081625 · NIAID · SEATTLE BIOMEDICAL RESEARCH INSTITUTE · PI STAMATATOS, LEONIDAS · 2010 to 2020
$5.8M
NIAID NIH HHS P01AI081625NIAID NIH HHS P01 AI094419NIAID NIH HHS P01AI094419NIAID NIH HHS P30 AI027757NIAID NIH HHS R01 AI081625
6 · The paper itself

Abstract

Vaccine candidates for HIV-1 so far have not been able to elicit broadly neutralizing antibodies (bNAbs) although they express the epitopes recognized by bNAbs to the HIV envelope glycoprotein (Env). To understand whether and how Env immunogens interact with the predicted germline versions of known bNAbs, we screened a large panel (N:56) of recombinant Envs (from clades A, B and C) for binding to the germline predecessors of the broadly neutralizing anti-CD4 binding site antibodies b12, NIH45-46 and 3BNC60. Although the mature antibodies reacted with diverse Envs, the corresponding germline antibodies did not display Env-reactivity. Experiments conducted with engineered chimeric antibodies combining the mature and germline heavy and light chains, respectively and vice-versa, revealed that both antibody chains are important for the known cross-reactivity of these antibodies. Our results also indicate that in order for b12 to display its broad cross-reactivity, multiple somatic mutations within its VH region are required. A consequence of the failure of the germline b12 to bind recombinant soluble Env is that Env-induced B-cell activation through the germline b12 BCR does not take place. Our study provides a new explanation for the difficulties in eliciting bNAbs with recombinant soluble Env immunogens. Our study also highlights the need for intense efforts to identify rare naturally occurring or engineered Envs that may engage the germline BCR versions of bNAbs.

Indexed as

AIDS VaccinesAntibodies, Anti-IdiotypicAntibodies, NeutralizingAntibody AffinityAntigens, ViralB-LymphocytesCD4 AntigensCell Lineenv Gene Products, Human Immunodeficiency VirusEpitopesHEK293 CellsHIV-1HIV AntibodiesHIV InfectionsHumansImmunoglobulin Heavy ChainsAIDS VaccinesAntibodies, Anti-IdiotypicAntibodies, NeutralizingAntigens, ViralCD4 Antigensenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesImmunoglobulin Heavy ChainsImmunoglobulin Light Chains

Identifiers

PMID23300456
PMCPMC3536657
OpenAlexW2093442592

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.