Evidence map›Paper›PMID 23066156›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

Anti-HIV B Cell lines as candidate vaccine biosensors.

Takayuki Ota, Colleen Doyle-Cooper, Anthony B Cooper, Michael Huber, Emilia Falkowska, Katherine J Doores, Lars Hangartner, Khoa Le, Devin Sok, Joseph Jardine and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

51 citing papers in PubMed, 59 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

20 authors at 8 institutions in 2 countries.

Takayuki OtaDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Colleen Doyle-Cooper
Anthony B Cooper
Michael Huber
Emilia Falkowska
Katherine J Doores
Lars Hangartner
Khoa Le
Devin Sok
Joseph Jardine
Jeffrey Lifson
Xueling Wu
John R Mascola
Pascal Poignard
James M Binley
Bimal K Chakrabarti
William R Schief
Richard T Wyatt
Dennis R Burton
David Nemazee
Scripps Research Institute · USUniversity of Zurich · CHFrederick National Laboratory for Cancer Research · USInternational AIDS Vaccine Initiative · USNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · USRagon Institute of MGH, MIT and Harvard · USTorrey Pines Institute For Molecular Studies · US

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MCELRATH, MARGARET JULIANA · 2012 to 2018
$131.5M
Pure and Authentic HIV-1 Env ImmunogensR01AI093278 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2011 to 2024
$11.6M
Interdisciplinary Tranining in Cancer ResearchT32CA080416 · NCI · UNIVERSITY OF WASHINGTON · PI STODDARD, BARRY L. · 1998 to 2023
$9.7M
Knock-in mice expressing germline-reverted broadly neutralizing HIV antibodiesR01AI073148 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI NEMAZEE, DAVID · 2007 to 2023
$8.2M
Probing the germlines of broadly neutralizing anti-HIV antibodies in knockin miceU01AI078224 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 2008 to 2012
$3.7M
Rescue of broadly neutralizing mAbs using native trimerR01AI100790 · NIAID · TORREY PINES INST FOR MOLECULAR STUDIES · PI BINLEY, JAMES M · 2012 to 2016
$2.3M
NCI NIH HHS T32 CA080416NIAID NIH HHS R01 AI073148NIAID NIH HHS R01 AI093278NIAID NIH HHS R01 AI100790NIAID NIH HHS U01 AI078224NIAID NIH HHS UM1 AI100663
6 · The paper itself

Abstract

Challenge studies following passive immunization with neutralizing Abs suggest that an HIV vaccine could be efficacious were it able to elicit broadly neutralizing Abs (bNAbs). To better understand the requirements for activation of B cells producing bNAbs, we generated cell lines expressing bNAbs or their germline-reverted versions (gl-bNAbs) as BCRs. We then tested the abilities of the bNAb-expressing cells to recognize HIV pseudovirions and vaccine candidate proteins by binding and activation assays. The results suggest that HIV envelope (Env) Ag-expressing, infection-competent virions are poorly recognized by high-affinity bNAb-expressing cells, as measured by the inability of Ags to induce rapid increases in intracellular calcium levels. Other Ag forms appear to be highly stimulatory, in particular, soluble gp140 trimers and a multimerized, scaffolded epitope protein. Virions failed to efficiently activate bNAb-expressing B cells owing to delayed or inefficient BCR recognition, most likely caused by the low density of Env spikes. Importantly, B cells carrying gl-bNAb BCRs were not stimulated by any of the tested vaccine candidates. These data provide insight into why many HIV immunogens, as well as natural HIV infections, fail to rapidly stimulate bNAb responses and suggest that bNAb-expressing cell lines might be useful tools in evaluation of vaccine Ags for infectious diseases. Because soluble Env trimers or multimerized scaffolded epitopes are best at activating B cell-expressing bNAbs, these antigenic forms should be considered as preferred vaccine components, although they should be modified to better target naive gl-bNAb B cells.

Indexed as

AIDS VaccinesAnimalsAntibodies, NeutralizingBiological AssayBiosensing TechniquesB-Lymphocytesenv Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV AntigensHumansMiceAIDS VaccinesAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency Virusgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesHIV Antigens

Identifiers

PMID23066156
PMCPMC3626558
OpenAlexW2146520916

What OpenQuestion holds

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LicenceTDM
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.