Evidence map›Paper›PMID 31841557›Full record

ArticlePLoS pathogens2019

IgG3 enhances neutralization potency and Fc effector function of an HIV V2-specific broadly neutralizing antibody.

Simone I Richardson, Bronwen E Lambson, Andrew R Crowley, Arman Bashirova, Cathrine Scheepers, Nigel Garrett, Salim Abdool Karim, Nonhlanhla N Mkhize, Mary Carrington, Margaret E Ackerman and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 97 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. The Impact of Pathogen Reduction on Total IgG and IgG Subclass Profiles of Convalescent Plasma.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2023
    Article
  20. Review

6 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

12 authors at 4 institutions in 2 countries.

Simone I RichardsonCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.ORCID 0000-0001-7678-2609
Bronwen E LambsonCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.
Andrew R CrowleyThayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.ORCID 0000-0002-5011-5362
Arman BashirovaRagon Institute of Massachusetts General Hospital, MIT, and Harvard University, Boston, Massachusetts, United States of America.
Cathrine ScheepersCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.ORCID 0000-0002-1683-0282
Nigel GarrettCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, KwaZulu-Natal, South Africa.ORCID 0000-0002-4530-234X
Salim Abdool KarimCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, KwaZulu-Natal, South Africa.ORCID 0000-0002-4986-2133
Nonhlanhla N MkhizeCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.ORCID 0000-0003-3037-1243
Mary CarringtonRagon Institute of Massachusetts General Hospital, MIT, and Harvard University, Boston, Massachusetts, United States of America.
Margaret E AckermanThayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.ORCID 0000-0002-4253-3476
Penny L MooreCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.ORCID 0000-0001-8719-4028
Lynn MorrisCentre for HIV and STI's, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.ORCID 0000-0003-3961-7828
University of the Witwatersrand · ZACentre for the AIDS Programme of Research in South Africa · ZADartmouth College · USRagon Institute of MGH, MIT and Harvard · US

Funding

The Viral Set Point in HIV-1 Subtype C InfectionU19AI051794 · NIAID · UNIVERSITY OF KWAZULU-NATAL · PI ABDOOL KARIM, SALIM S · 2002 to 2007
$22.5M
Physical Resources CoreP01AI120756 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2016 to 2020
$17.1M
Directing Antibody Effector Activity via Controlled IgG Subclass SwitchingR01AI131975 · NIAID · DARTMOUTH COLLEGE · PI ACKERMAN, MARGARET E · 2017 to 2020
$2.6M
Evolution of glycan-reactive broadly neutralizing anti-v2 antibodies in HIV infecR01AI104387 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI MORRIS, LYNN · 2013 to 2016
$2.0M
Immunoglobulin gene diversity in an African population and impact on antibody function in HIV infectionU01AI136677 · NIAID · WITS HEALTH CONSORTIUM (PTY), LTD · PI MORRIS, LYNN · 2017 to 2021
$1.2M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENIAID NIH HHS P01 AI120756NIAID NIH HHS R01 AI104387NIAID NIH HHS R01 AI131975NIAID NIH HHS U01 AI136677NIAID NIH HHS U19 AI051794
6 · The paper itself

Abstract

Broadly neutralizing antibodies (bNAbs) protect against HIV infection in non-human primates and their efficacy may be enhanced through interaction with Fc receptors on immune cells. Antibody isotype is a modulator of this binding with the IgG3 subclass mediating potent Fc effector function and is associated with HIV vaccine efficacy and HIV control. BNAb functions are typically assessed independently of the constant region with which they are naturally expressed. To examine the role of natural isotype in the context of a bNAb lineage we studied CAP256, an HIV-infected individual that mounted a potent V2-specific bNAb response. CAP256 expressed persistently high levels of plasma IgG3 which we found mediated both broad neutralizing activity and potent Fc function. Sequencing of germline DNA and the constant regions of V2-directed bNAbs from this donor revealed the expression of a novel IGHG3 allele as well as IGHG3*17, an allele that produces IgG3 antibodies with increased plasma half-life. Both allelic variants were used to generate CAP256-VRC26.25 and CAP256-VRC26.29 IgG3 bNAbs and these were compared to IgG1 versions. IgG3 variants were shown to have significantly higher phagocytosis and trogocytosis compared to IgG1 versions, which corresponded to increased affinity for FcγRIIa. Neutralization potency was also significantly higher for IgG3 bNAbs, particularly against viruses lacking the N160 glycan. By exchanging hinge regions between subclass variants, we showed that hinge length modulated both neutralization potency and Fc function. This study showed that co-operation between the variable and natural IgG3 constant regions enhanced the polyfunctionality of antibodies, indicating the value of leveraging genetic variation which could be exploited for passive immunity.

Indexed as

AdultAIDS VaccinesBroadly Neutralizing AntibodiesFemaleHIV AntibodiesHIV InfectionsHumansImmunoglobulin GImmunoglobulin IsotypesReceptors, FcAIDS VaccinesBroadly Neutralizing AntibodiesHIV AntibodiesImmunoglobulin GImmunoglobulin IsotypesReceptors, Fc

Identifiers

PMID31841557
PMCPMC6936867
OpenAlexW2995164637

What OpenQuestion holds

Textmetadata
LicenceCC0
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.