ArticleJournal of virology2012
Increased antibody affinity confers broad in vitro protection against escape mutants of severe acute respiratory syndrome coronavirus.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Identification of Two Competition-Defined Neutralizing Antibody Groups Targeting the HHV-6B gH/gL/gQ1/gQ2 Complex Independent of CD134 Binding.Microbiology and immunology · 2026Article
- Magnetic bead-based electrochemical surrogate virus neutralization test for quantification of antibody neutralizing efficiency.Biosensors & bioelectronics · 2025Article
- RESP2: An Uncertainty Aware Multi-Target Multi-Property Optimization AI Pipeline for Antibody Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Antibody avidity, persistence, and response to antigen recall: comparison of vaccine adjuvants.NPJ vaccines · 2021Article
- Selection, identification, and characterization of SARS-CoV-2 monoclonal antibody resistant mutants.Journal of virological methods · 2021Article
- A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19.SN comprehensive clinical medicine · 2020Review
- Applying Immune Instincts and Maternal Intelligence from Comparative Microbiology to COVID-19.SN comprehensive clinical medicine · 2020Review
- Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms.Toxins · 2019Article
- Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform.Journal of virology · 2018Article
- Toward Developing a Preventive MERS-CoV Vaccine-Report from a Workshop Organized by the Saudi Arabia Ministry of Health and the International Vaccine Institute, Riyadh, Saudi Arabia, November 14-15, 2015.Emerging infectious diseases · 2016Article
- Reconstitution of the receptor-binding motif of the SARS coronavirus.Protein engineering, design & selection : PEDS · 2015Article
- Structural flexibility of a conserved antigenic region in hepatitis C virus glycoprotein E2 recognized by broadly neutralizing antibodies.Journal of virology · 2015Article
- Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness.Journal of virology · 2014Article
- Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5.Proteins · 2014Article
- Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Severe acute respiratory syndrome: a vanished evil?Journal of thoracic disease · 2013Article
- Human monoclonal antibodies as candidate therapeutics against emerging viruses and HIV-1.Virologica Sinica · 2013Review
- Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- A dual-mode surface display system for the maturation and production of monoclonal antibodies in glyco-engineered Pichia pastoris.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (K(D)) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.
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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.