Evidence map›Paper›PMID 26267277›Full record

ArticlePLoS pathogens2015

Incomplete Neutralization and Deviation from Sigmoidal Neutralization Curves for HIV Broadly Neutralizing Monoclonal Antibodies.

Laura E McCoy, Emilia Falkowska, Katie J Doores, Khoa Le, Devin Sok, Marit J van Gils, Zelda Euler, Judith A Burger, Michael S Seaman, Rogier W Sanders and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

74 citing papers in PubMed, 90 citations in OpenAlex.

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  20. Principles of SARS-CoV-2 glycosylation.Current opinion in structural biology · 2022
    Review

14 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

14 authors at 7 institutions in 3 countries.

Laura E McCoyDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America.
Emilia FalkowskaDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America.
Katie J DooresDepartment of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London, United Kingdom.
Khoa LeDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America.
Devin SokDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America.
Marit J van GilsLaboratory of Viral Immunopathogenesis, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Zelda EulerLaboratory of Viral Immunopathogenesis, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Judith A BurgerLaboratory of Viral Immunopathogenesis, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Michael S SeamanBeth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
Rogier W SandersLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Hanneke SchuitemakerLaboratory of Viral Immunopathogenesis, Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Pascal PoignardDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America.
Terri WrinMonogram Biosciences, Inc., South San Francisco, California, United States of America.
Dennis R BurtonDepartment of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America.
Academic Medical Center · NLScripps Research Institute · USInternational AIDS Vaccine Initiative · USUniversity of Amsterdam · NLBeth Israel Deaconess Medical Center · USGuy's Hospital · GBRagon Institute of MGH, MIT and Harvard · US

Funding

Support Component D/Vaccine Discovery, Concept to ClinicUM1AI100663 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI MCELRATH, MARGARET JULIANA · 2012 to 2018
$131.5M
HUMAN ANTIBODIES TO HIV-1 BY REPERTOIRE CLONINGR01AI033292 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI BURTON, DENNIS R. · 1992 to 2013
$5.9M
NIAID NIH HHS R01 AI033292NIAID NIH HHS UM1 AI100663NIAID NIH HHS UM1AI100663
6 · The paper itself

Abstract

The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingHEK293 CellsHIV-1HIV AntibodiesHumansNeutralization TestsAntibodies, MonoclonalAntibodies, NeutralizingHIV Antibodies

Identifiers

PMID26267277
PMCPMC4534392
OpenAlexW2133367683

What OpenQuestion holds

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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.