ArticleCell2015
Intra-spike crosslinking overcomes antibody evasion by HIV-1.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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.
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.
Who cites it
87 citing papers in PubMed.
- Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.Communications biology · 2025Article
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- Bispecific antibodies against the hepatitis C virus E1E2 envelope glycoprotein.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Different Fc scaffolds enhance the breadth ofFrontiers in immunology · 2025Article
- Viral glycoprotein-mediated entry and antibody-mediated immunity in HIV-1 and SARS-CoV-2 infection.Frontiers in immunology · 2025Review
- Intra-channel bi-epitopic crosslinking unleashes ultrapotent antibodies targeting NaCell reports. Medicine · 2024Article
- Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection.PLoS pathogens · 2024Article
- Minimal Determinants for Lifelong Antiviral Antibody Responses in Mice from a Single Exposure to Virus-like Immunogens at Low Doses.Vaccines · 2024Article
- Neutralizing the threat: harnessing broadly neutralizing antibodies against HIV-1 for treatment and prevention.Microbial cell (Graz, Austria) · 2024Article
- Article
- Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility.Nature communications · 2023Article
- Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by reducing signaling activity through epitope selection.Communications biology · 2023Article
- Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein.JACS Au · 2023Article
- Orchestrating Binding Interactions and the Emergence of Avidity Driven Therapeutics.ACS central science · 2023Article
- Antibody class-switching as a strategy to improve HIV-1 neutralization.Trends in molecular medicine · 2022Review
- Polyvalent Glycan Quantum Dots as a Multifunctional Tool for Revealing Thermodynamic, Kinetic, and Structural Details of Multivalent Lectin-Glycan Interactions.ACS applied materials & interfaces · 2022Article
- Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth.Nature communications · 2022Article
- IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2.The Journal of experimental medicine · 2022Article
- Single-Chain Variable Fragments of Broadly Neutralizing Antibodies Prevent HIV Cell-Cell Transmission.Journal of virology · 2022Article
- The Hidden Side of Complement Regulator C4BP: Dissection and Evaluation of Its Immunomodulatory Activity.Frontiers in immunology · 2022Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV's low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a "molecular ruler" to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders of magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection.
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What OpenQuestion holds
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.