Evidence map›Paper›PMID 37251375›Full record

ArticleFrontiers in immunology2023

Enhancing the therapeutic activity of hyperimmune IgG against chikungunya virus using FcγRIIIa affinity chromatography.

Julie M Fox, Vicky Roy, Bronwyn M Gunn, Glen R Bolton, Daved H Fremont, Galit Alter, Michael S Diamond, Austin W Boesch

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
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

8 authors at 3 institutions in 1 country.

Julie M FoxDepartment of Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Vicky RoyRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard University, Cambridge, MA, United States.
Bronwyn M GunnRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard University, Cambridge, MA, United States.
Glen R BoltonZepteon, Inc., Boston, MA, United States.
Daved H FremontDepartment of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United States.
Galit AlterRagon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), and Harvard University, Cambridge, MA, United States.
Michael S DiamondDepartment of Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Austin W BoeschZepteon, Inc., Boston, MA, United States.
Ragon Institute of MGH, MIT and Harvard · USWashington University in St. Louis · USNational Institute of Allergy and Infectious Diseases · US

Funding

Infectious Diseases/Basic Microbial Pathogenic MechanismsT32AI007172 · NIAID · WASHINGTON UNIVERSITY · PI Daniel E. Goldberg, JENNIFER A PHILIPS · 1985 to 2026
$13.0M
COVID Supplement B Cell Epitope Discovery and Mechanisms of Antibody Protection.75N93019C00062 · NIAID · WASHINGTON UNIVERSITY · PI FREMONT, DAVED · 2019 to 2023
$11.7M
Mechanisms of immune-mediated protection and pathogenesis during viral infectionsZIAAI001348 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FOX, JULIE · 2021 to 2025
$7.4M
Antibody Based Therapeuticcs for Chikungunya VirusR01AI089591 · NIAID · WASHINGTON UNIVERSITY · PI DIAMOND, MICHAEL S · 2010 to 2014
$4.7M
Structural and functional basis of ultra potent CHKV neutralization by human mAbsR01AI114816 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CROWE, JAMES E, DIAMOND, MICHAEL S · 2015 to 2019
$3.7M
NIAID NIH HHS 75N93019C00062NIAID NIH HHS R01 AI089591NIAID NIH HHS R01 AI114816NIAID NIH HHS T32 AI007172
6 · The paper itself

Abstract

Introduction: Chikungunya virus (CHIKV) is a re-emerging mosquito transmitted alphavirus of global concern. Neutralizing antibodies and antibody Fc-effector functions have been shown to reduce CHIKV disease and infection in animals. However, the ability to improve the therapeutic activity of CHIKV-specific polyclonal IgG by enhancing Fc-effector functions through modulation of IgG subclass and glycoforms remains unknown. Here, we evaluated the protective efficacy of CHIKV-immune IgG enriched for binding to Fc-gamma receptor IIIa (FcγRIIIa) to select for IgG with enhanced Fc effector functions. Methods: Total IgG was isolated from CHIKV-immune convalescent donors with and without additional purification by FcγRIIIa affinity chromatography. The enriched IgG was characterized in biophysical and biological assays and assessed for therapeutic efficacy during CHIKV infection in mice. Results: FcγRIIIa-column purification enriched for afucosylated IgG glycoforms. In vitro characterization showed the enriched CHIKV-immune IgG had enhanced human FcγRIIIa and mouse FcγRIV affinity and FcγR-mediated effector function without reducing virus neutralization in cellular assays. When administered as post-exposure therapy in mice, CHIKV-immune IgG enriched in afucosylated glycoforms promoted reduction in viral load. Discussion: Our study provides evidence that, in mice, increasing Fc engagement of FcγRs on effector cells, by leveraging FcγRIIIa-affinity chromatography, enhanced the antiviral activity of CHIKV-immune IgG and reveals a path to produce more effective therapeutics against these and potentially other emerging viruses.

Indexed as

Chikungunya FeverChikungunya virusAnimalsAntibodies, ViralChromatography, AffinityHumansImmunoglobulin GMiceReceptors, IgGAntibodies, ViralImmunoglobulin GReceptors, IgGafucosylatedantibody effector functionchikungunya viruschromatographyFcγRIIIaglycoformhyperimmune IgG

Identifiers

PMID37251375
PMCPMC10213286
OpenAlexW4376280186

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.