ArticleFrontiers in immunology2021
HIV Broadly Neutralizing Antibodies Expressed as IgG3 Preserve Neutralization Potency and Show Improved Fc Effector Function.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Extended hinge length of human IgG3-like antibody enhances early antiviral activity of VRC01 in SHIV-infected rhesus macaques.Journal of virology · 2026Article
- mGem: Opening Env and harnessing NK cell effector functions to eliminate HIV-1-infected cells.mBio · 2026Review
- Functional Activity of HIV-1 bNAbs Across Diverse Strains is Driven by Binding Site and Can be Enhanced Through Fc Engineering.bioRxiv : the preprint server for biology · 2025Article
- Augmented humoral responses to HIV Env trimers delivered as transmembrane immunogens by self-replicating RNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A modification to heptad repeat 1 of gp41 improves yield and/or quality of soluble pre-fusion HIV-1 envelope glycoprotein trimers.Journal of virology · 2025Article
- Vaginal microbiome dysbiosis and sexually transmitted infections correlate with concentrations of immunoglobulin isotypes in human cervicovaginal mucus: insights into HIV-1 transmission.Frontiers in immunology · 2025Article
- Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment.Oncology research · 2025Review
- Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 2025Article
- 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 · 2023Article
- Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility.Nature communications · 2023Article
- Antiviral neutralizing antibodies: from in vitro to in vivo activity.Nature reviews. Immunology · 2023Review
- Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations.Frontiers in immunology · 2023Review
- Antibody class-switching as a strategy to improve HIV-1 neutralization.Trends in molecular medicine · 2022Review
- Enhanced neutralization potency of an identical HIV neutralizing antibody expressed as different isotypes is achieved through genetically distinct mechanisms.Scientific reports · 2022Article
- Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys.Nature microbiology · 2022Article
- Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Challenges and Opportunities of Therapies Targeting Early Life Immunity for Pediatric HIV Cure.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of several broadly neutralizing antibodies (bNAbs) to protect against HIV infection is enhanced through Fc receptor binding. Antibody isotype modulates this effect, with IgG3 associated with improved HIV control and vaccine efficacy. We recently showed that an IgG3 variant of bNAb CAP256-VRC26.25 exhibited more potent neutralization and phagocytosis than its IgG1 counterpart. Here, we expanded this analysis to include additional bNAbs targeting all major epitopes. A total of 15 bNAbs were expressed as IgG1 or IgG3, and pairs were assessed for neutralization potency against the multi-subtype global panel of 11 HIV strains. Binding to the neonatal Fc receptor (FcRn) and Fcγ receptors were measured using ELISA and antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis were measured using infectious viruses and global panel Env SOSIP trimers, respectively. IgG3 bNAbs generally showed similar or increased (up to 60 fold) neutralization potency than IgG1 versions, though the effect was virus-specific. This improvement was statistically significant for CAP256-VRC26.25, 35022, PGT135 and CAP255.G3. IgG3 bNAbs also showed significantly improved binding to FcγRIIa which correlated with enhanced phagocytosis of all trimeric Env antigens. Differences in ADCC were epitope-specific, with IgG3 bNAbs to the MPER, CD4 binding site and gp120-gp41 interface showing increased ADCC. We also explored the pH dependence of IgG1 and IgG3 variants for FcRn binding, as this determines the half-life of antibodies. We observed reduced pH dependence, associated with shorter half-lives for IgG3 bNAbs, with κ-light chains. However, IgG3 bNAbs that use λ-light chains showed similar pH dependence to their IgG1 counterparts. This study supports the manipulation of the constant region to improve both the neutralizing and Fc effector activity of bNAbs, and suggests that IgG3 versions of bNAbs may be preferable for passive immunity given their polyfunctionality.
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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.