Evidence map›Paper›PMID 34579568›Full record

ArticlemBio2021

Across Functional Boundaries: Making Nonneutralizing Antibodies To Neutralize HIV-1 and Mediate Fc-Mediated Effector Killing of Infected Cells.

Jonathan Richard, Dung N Nguyen, William D Tolbert, Romain Gasser, Shilei Ding, Dani Vézina, Shang Yu Gong, Jérémie Prévost, Gabrielle Gendron-Lepage, Halima Medjahed and 3 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

8 citing papers in PubMed, 14 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

13 authors at 2 institutions in 2 countries.

Jonathan Richard *Centre de Recherche du CHUM, Montréal, Québec, Canada.
Dung N Nguyen *Infectious Disease Division, Department of Medicine of Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
William D TolbertInfectious Disease Division, Department of Medicine of Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
Romain GasserCentre de Recherche du CHUM, Montréal, Québec, Canada.
Shilei DingCentre de Recherche du CHUM, Montréal, Québec, Canada.
Dani VézinaCentre de Recherche du CHUM, Montréal, Québec, Canada.ORCID 0000-0002-0780-8593
Shang Yu GongCentre de Recherche du CHUM, Montréal, Québec, Canada.
Jérémie PrévostCentre de Recherche du CHUM, Montréal, Québec, Canada.
Gabrielle Gendron-LepageCentre de Recherche du CHUM, Montréal, Québec, Canada.
Halima MedjahedCentre de Recherche du CHUM, Montréal, Québec, Canada.
Suneetha GottumukkalaInfectious Disease Division, Department of Medicine of Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.
Andrés FinziCentre de Recherche du CHUM, Montréal, Québec, Canada.ORCID 0000-0002-4992-5288
Marzena PazgierInfectious Disease Division, Department of Medicine of Uniformed Services University of the Health Sciencesgrid.265436.0, Bethesda, Maryland, USA.ORCID 0000-0003-0594-5057
Centre Hospitalier de l’Université de Montréal · CAUniformed Services University of the Health Sciences · US

Funding

Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01GM056550 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI ABRAMS, CAMERON F · 1997 to 2018
$31.2M
Physical Resources CoreP01AI120756 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2016 to 2020
$17.1M
Understanding Envelope Function in HIV-1 Infection: The Design, Synthesis and Validation of Small Molecule HIV-1 Env InhibitorsP01AI150471 · NIAID · DREXEL UNIVERSITY · PI HENDRICKSON, WAYNE A. · 2019 to 2022
$7.8M
Computational models of naturally acquired immunity to falciparum malariaU01AI150741 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BUTTE, ATUL J, GREENHOUSE, BRYAN R · 2020 to 2024
$7.4M
Exploring HIV-1 Env open conformations for therapeutic interventionR01AI150322 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Andres Finzi, James B Munro · 2020 to 2026
$4.2M
Unlocking Envelope: A New Strategy for a Functional Cure Through Antibody-Dependent Cell-Mediated CytotoxicityR01AI129769 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PAZGIER, MARZENA ELZBIETA · 2017 to 2021
$2.3M
Structural Targeting of Potentially Protective gp120 Epitopes in the C1/C2 RegionR01AI116274 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI PAZGIER, MARZENA ELZBIETA · 2016 to 2019
$1.5M
CIHR 352417NIAID NIH HHS P01 AI120756NIAID NIH HHS P01 AI150471NIAID NIH HHS R01 AI116274NIAID NIH HHS R01 AI129769NIAID NIH HHS R01 AI150322NIAID NIH HHS U01 AI150741NIGMS NIH HHS P01 GM056550
6 · The paper itself

Abstract

In HIV-1 infection, many antibodies (Abs) are elicited to Envelope (Env) epitopes that are conformationally masked in the native trimer and are only available for antibody recognition after the trimer binds host cell CD4. Among these are epitopes within the Co-Receptor Binding Site (CoRBS) and the constant region 1 and 2 (C1-C2 or cluster A region). In particular, C1-C2 epitopes map to the gp120 face interacting with gp41 in the native, "closed" Env trimer present on HIV-1 virions or expressed on HIV-1-infected cells. Antibodies targeting this region are therefore nonneutralizing and their potential as mediators of antibody-dependent cellular cytotoxicity (ADCC) of HIV-1-infected cells diminished by a lack of available binding targets. Here, we present the design of Ab-CD4 chimeric proteins that consist of the Ab-IgG1 of a CoRBS or cluster A specificity to the extracellular domains 1 and 2 of human CD4. Our Ab-CD4 hybrids induce potent ADCC against infected primary CD4

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityCD4 AntigensCD4-Positive T-LymphocytesEpitopesHIV-1HIV AntibodiesHumansNeutralization TestsProtein BindingAntibodies, MonoclonalAntibodies, NeutralizingCD4 AntigensEpitopesHIV AntibodiesAb-CD4 hybridsADCCHIV-1neutralizationnonneutralizing antibodies

Identifiers

PMID34579568
PMCPMC8546553
OpenAlexW3204633974

What Socratic 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 Socratic graph.