Evidence map›Paper›PMID 25522326›Full record

ArticlePLoS pathogens2014

Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.

Laura E McCoy, Lucy Rutten, Dan Frampton, Ian Anderson, Luke Granger, Rachael Bashford-Rogers, Gillian Dekkers, Nika M Strokappe, Michael S Seaman, Willie Koh and 6 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

30 citing papers in PubMed, 46 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 8 institutions in 5 countries.

Laura E McCoyWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Lucy RuttenQVQ B.V., Utrecht, The Netherlands.
Dan FramptonWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Ian AndersonWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Luke GrangerDepartment of Infectious Diseases, King's College London School of Medicine, Guy's Hospital, London, United Kingdom.
Rachael Bashford-RogersWellcome Trust Sanger Institute, Cambridge, United Kingdom.
Gillian DekkersWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Nika M StrokappeQVQ B.V., Utrecht, The Netherlands.
Michael S SeamanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Willie KohWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Vanina GrippoCentro de Virología Animal, Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Alexander KlicheInstitute of Medical Microbiology, University of Regensburg, Regensburg, Germany.
Theo VerripsQVQ B.V., Utrecht, The Netherlands.
Paul KellamWellcome Trust Sanger Institute, Cambridge, United Kingdom.
Ariberto FassatiWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Robin A WeissWohl Virion Centre and Medical Research Council (MRC) Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom.
Medical Research Council · GBQserve Group (Netherlands) · NLUniversity College London · GBWellcome Sanger Institute · GBBeth Israel Deaconess Medical Center · USConsejo Nacional de Investigaciones Científicas y Técnicas · ARKing's College London · GBUniversity of Regensburg · DE

Funding

Medical Research Council G0900950Medical Research Council MC_EX_G0800785
6 · The paper itself

Abstract

To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.

Indexed as

Evolution, MolecularAIDS VaccinesAnimalsAntibodies, NeutralizingAntigens, ViralBinding Sites, AntibodyCamelids, New WorldCD4 AntigensDisease Models, AnimalHIV-1HIV InfectionsImmunoglobulin Variable RegionMutationAIDS VaccinesAntibodies, NeutralizingAntigens, ViralCD4 AntigensImmunoglobulin Variable Region

Identifiers

PMID25522326
PMCPMC4270772
OpenAlexW2159047076

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.