Evidence map›Paper›PMID 22875963›Full record

ArticleJournal of virology2012

HIV-1 neutralizing antibodies display dual recognition of the primary and coreceptor binding sites and preferential binding to fully cleaved envelope glycoproteins.

Yuxing Li, Sijy O'Dell, Richard Wilson, Xueling Wu, Stephen D Schmidt, Carl-Magnus Hogerkorp, Mark K Louder, Nancy S Longo, Christian Poulsen, Javier Guenaga and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

50 citing papers in PubMed, 61 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

16 authors at 3 institutions in 1 country.

Yuxing LiVaccine Research Center, NIAID, NIH, Bethesda, Maryland, USA.
Sijy O'Dell
Richard Wilson
Xueling Wu
Stephen D Schmidt
Carl-Magnus Hogerkorp
Mark K Louder
Nancy S Longo
Christian Poulsen
Javier Guenaga
Bimal K Chakrabarti
Nicole Doria-Rose
Mario Roederer
Mark Connors
John R Mascola
Richard T Wyatt
Scripps Research Institute · USNational Institute of Allergy and Infectious Diseases · USInternational AIDS Vaccine Initiative · US

Funding

Mechanisms of Effective Humoral Immune Responses to HIV-1ZIAAI001090 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CONNORS, MARK · 2009 to 2025
$14.8M
Isolation of Monoclonal Antiobodies Against HIVZIAAI005095 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DORIA-ROSE, NICOLE · 2009 to 2025
$14.5M
Determination of the Neutralization Specificity in Broadly Neutralizing HIV SeraZIAAI005089 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MASCOLA, JOHN · 2009 to 2018
$9.6M
Measurement of HIV Neutralization Using Quantitative AssaysZIAAI005010 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MASCOLA, JOHN · 2009 to 2018
$7.6M
Preclinical Evaluation Of Neutralizing Antibodies Elicited by HIV-1 ImmunogensZIAAI005012 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MASCOLA, JOHN · 2009 to 2018
$7.1M
Identification of HIV-specific B cells in bloodZIAAI005067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ROEDERER, MARIO · 2009 to 2014
$3.0M
Intramural NIH HHS
6 · The paper itself

Abstract

The gp120 CD4 binding site (CD4bs) and coreceptor binding site (CoRbs) are two functionally conserved elements of the HIV-1 envelope glycoproteins (Env). We previously defined the presence of CD4bs-neutralizing antibodies in the serum of an HIV-1-infected individual and subsequently isolated the CD4bs-specific monoclonal antibodies (MAbs) VRC01 and VRC03 from the memory B cell population. Since this donor's serum also appeared to contain neutralizing antibodies to the CoRbs, we employed a differential fluorescence-activated cell sorter (FACS)-based sorting strategy using an Env trimer possessing a CoRbs knockout mutation (I420R) to isolate specific B cells. The MAb VRC06 was recovered from these cells, and its genetic sequence allowed us to identify a clonal relative termed VRC06b, which was isolated from a prior cell sort using a resurfaced core gp120 probe and its cognate CD4bs knockout mutant. VRC06 and VRC06b neutralized 22% and 44% of viruses tested, respectively. Epitope mapping studies revealed that the two MAbs were sensitive to mutations in both the gp120 CoRbs and the CD4bs and could cross-block binding of both CD4bs and CoRbs MAbs to gp120. Fine mapping indicated contacts within the gp120 bridging sheet and the base of the third major variable region (V3), which are elements of the CoRbs. Cell surface binding assays demonstrated preferential recognition of fully cleaved Env trimers over uncleaved trimers. Thus, VRC06 and VRC06b are Env trimer precursor cleavage-sensitive neutralizing MAbs that bind to a region of gp120 that overlaps both the primary and the secondary HIV-1 receptor binding sites.

Indexed as

Binding Sites, AntibodyAntibodies, MonoclonalAntibodies, NeutralizingB-LymphocytesCD4 AntigensCells, CulturedEpitope MappingEpitopesHIV-1HIV AntibodiesHIV Envelope Protein gp120HumansImmunoglobulin GMutationReceptors, HIVAntibodies, MonoclonalAntibodies, NeutralizingCD4 AntigensEpitopesHIV AntibodiesHIV Envelope Protein gp120Immunoglobulin GReceptors, HIV

Identifiers

PMID22875963
PMCPMC3457177
OpenAlexW2108104660

What OpenQuestion holds

Textmetadata
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.