ArticleScientific reports2022
Enhanced neutralization potency of an identical HIV neutralizing antibody expressed as different isotypes is achieved through genetically distinct mechanisms.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Serum IgA proteomics reveals clonal composition and neutralization of dimeric and monomeric IgA repertoires against human norovirus.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell-free RNA reveals host and microbial correlates of broadly neutralizing antibody development against HIV.PLoS pathogens · 2026Article
- Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.Current HIV research · 2026Review
- Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 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
- Induction of Tier 2 HIV-Neutralizing IgA Antibodies in Rhesus Macaques Vaccinated with BG505.664 SOSIP.Vaccines · 2024Article
- Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families.PLoS pathogens · 2024Article
- Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.Clinical microbiology reviews · 2024Review
- Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus.Communications biology · 2024Article
- 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
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Antibodies with the same variable region can exist as multiple isotypes with varying neutralization potencies, though the mechanism for this is not fully defined. We previously isolated an HIV-directed IgA1 monoclonal antibody (mAb), CAP88-CH06, and showed that IgA1 and IgG3 isotypes of this antibody demonstrated enhanced neutralization compared to IgG1. To explore the mechanism behind this, hinge region and constant heavy chain (CH1) chimeras were constructed between the IgA1, IgG3 and IgG1 mAbs and assessed for neutralization activity, antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC). Hinge chimeras revealed that the increased neutralization potency and phagocytosis of the IgG3 isotype was attributed to its longer hinge region. In contrast, for IgA1, CH1 chimeras showed that this region was responsible both for enhanced neutralization potency and decreased ADCP, though ADCC was not affected. Overall, these data show that the enhanced neutralization potency of CAP88-CH06 IgG3 and IgA1, compared to IgG1, is achieved through distinct mechanisms. Understanding the influence of the hinge and CH1 regions on Fab domain function may provide insights into the engineering of therapeutic antibodies with increased neutralization potency.
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