ArticleCell systems2019
Harnessing Avidity: Quantifying the Entropic and Energetic Effects of Linker Length and Rigidity for Multivalent Binding of Antibodies to HIV-1.
Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed.
- Article
- Antigen flexibility supports the avidity of hemagglutinin-specific antibodies at low antigen densities.PLoS pathogens · 2026Article
- Article
- Article
- An Antibody Cocktail-Based Immunoaffinity-LC-MS Method Enabled Ultra-Sensitive and Robust Quantification of Circulating Proinsulin Proteoforms and C-Peptide.Analytical chemistry · 2025Article
- Identification of a broad and potent V3 glycan site bNAb targeting an N332bioRxiv : the preprint server for biology · 2025Article
- Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 2025Article
- A Multivalent DNA Nanoparticle/Peptide Hybrid Molecular Modality for the Modulation of Protein-Protein Interactions in the Tumor Microenvironment.Advanced nanobiomed research · 2024Article
- Bioluminescent detection of viral surface proteins using branched multivalent protein switches.RSC chemical biology · 2024Article
- Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.Nature communications · 2024Article
- Orchestrating Binding Interactions and the Emergence of Avidity Driven Therapeutics.ACS central science · 2023Article
- A covalent opsonization approach to enhance synthetic immunity against viral escape variants.Cell reports. Physical science · 2023Article
- How cells wrap around virus-like particles using extracellular filamentous protein structures.bioRxiv : the preprint server for biology · 2023Article
- How cells wrap around virus-like particles using extracellular filamentous protein structures.ArXiv · 2023Article
- Antibody class-switching as a strategy to improve HIV-1 neutralization.Trends in molecular medicine · 2022Review
- Ultrapotent and broad neutralization of SARS-CoV-2 variants by modular, tetravalent, bi-paratopic antibodies.Cell reports · 2022Article
- Structural and Computational Studies of the SARS-CoV-2 Spike Protein Binding Mechanisms with Nanobodies: From Structure and Dynamics to Avidity-Driven Nanobody Engineering.International journal of molecular sciences · 2022Review
- Article
- When two are better than one: Modeling the mechanisms of antibody mixtures.PLoS computational biology · 2020Article
- Binding Revisited-Avidity in Cellular Function and Signaling.Frontiers in molecular biosciences · 2020Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
IgG antibodies increase their apparent affinities by using both of their Fabs to simultaneously attach to antigens. HIV-1 foils this strategy by having few, and highly separated, Envelope (Env) spike targets for antibodies, forcing most IgGs to bind monovalently. Here, we develop a statistical mechanics model of synthetic diFabs joined by DNA linkers of different lengths and flexibilities. This framework enables us to translate the energetic and entropic effects of the linker into the neutralization potency of a diFab. We demonstrate that the strongest neutralization potencies are predicted to require a rigid linker that optimally spans the distance between two Fab binding sites on an Env trimer and that avidity can be further boosted by incorporating more Fabs into these constructs. These results inform the design of multivalent anti-HIV-1 therapeutics that utilize avidity effects to remain potent against HIV-1 in the face of the rapid mutation of Env spikes.
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Registered trials
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.