ArticlePLoS pathogens2020
Hinge length contributes to the phagocytic activity of HIV-specific IgG1 and IgG3 antibodies.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 83 citations in OpenAlex.
- Candidate correlates of protection in the HVTN505 HIV-1 vaccine efficacy trial identified by positive-unlabeled learning.PLoS computational biology · 2025Trial
- Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients.Signal transduction and targeted therapy · 2021Trial
- Why antibody isotype matters for immunotherapy.Antibody therapeutics · 2026Review
- Extended hinge length of human IgG3-like antibody enhances early antiviral activity of VRC01 in SHIV-infected rhesus macaques.Journal of virology · 2026Article
- GATHeR: graph-based accurate tool for immunoglobulin heavy- and light-chain reconstruction.Nature communications · 2026Article
- Key Role of Pro230 in the Hinge Region on the Architecture and Function of IgG1.Journal of medicinal chemistry · 2026Article
- Article
- Eliminating interactions with the viral Fc receptor improves antibody-mediated protection against neonatal HSV infection in mice.Science translational medicine · 2025Article
- Effects and mechanisms of monoclonal and polyclonal human antibodies in protection of humanized mice from HIV-1 challenge.bioRxiv : the preprint server for biology · 2025Article
- 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
- Association of a Novel IgG3 Allele With Malaria in Children From the Sepik Region of Papua New Guinea.The Journal of infectious diseases · 2025Article
- Candidate Correlates of Protection in the HVTN505 HIV-1 Vaccine Efficacy Trial Identified by Positive-Unlabeled Learning.medRxiv : the preprint server for health sciences · 2025Article
- Functional and phenotypic profiles of HLA-specific antibodies in relation to antibody-mediated kidney transplant rejection.Human immunology · 2025Article
- Dissecting the properties of circulating IgG against streptococcal pathogens through a combined systems antigenomics-serology workflow.Nature communications · 2025Article
- Review
- Cross-species analysis of FcγRIIa/b (CD32a/b) polymorphisms at position 131: structural and functional insights into the mechanism of IgG- mediated phagocytosis in human and macaque.Frontiers in immunology · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Potent broadly neutralizing antibodies mediate efficient antibody-dependent phagocytosis of HIV-infected cells.PLoS pathogens · 2024Article
- Lupus IgA1 autoantibodies synergize with IgG to enhance plasmacytoid dendritic cell responses to RNA-containing immune complexes.Science translational medicine · 2024Article
- Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.Clinical microbiology reviews · 2024Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Antibody functions such as neutralization require recognition of antigen by the Fab region, while effector functions are additionally mediated by interactions of the Fc region with soluble factors and cellular receptors. The efficacy of individual antibodies varies based on Fab domain characteristics, such as affinity for antigen and epitope-specificity, and on Fc domain characteristics that include isotype, subclass, and glycosylation profile. Here, a series of HIV-specific antibody subclass and hinge variants were constructed and tested to define those properties associated with differential effector function. In the context of the broadly neutralizing CD4 binding site-specific antibody VRC01 and the variable loop (V3) binding antibody 447-52D, hinge truncation and extension had a considerable impact on the magnitude of phagocytic activity of both IgG1 and IgG3 subclasses. The improvement in phagocytic potency of antibodies with extended hinges could not be attributed to changes in either intrinsic antigen or antibody receptor affinity. This effect was specific to phagocytosis and was generalizable to different phagocytes, at different effector cell to target ratios, for target particles of different size and composition, and occurred across a range of antibody concentrations. Antibody dependent cellular cytotoxicity and neutralization were generally independent of hinge length, and complement deposition displayed variable local optima. In vivo stability testing showed that IgG molecules with altered hinges can exhibit similar biodistribution and pharmacokinetic profiles as IgG1. Overall, these results suggest that when high phagocytic activity is desirable, therapeutic antibodies may benefit from being formatted as human IgG3 or engineered IgG1 forms with elongated hinges.
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