ArticleChemistry & biology2015
Depletion of T cell epitopes in lysostaphin mitigates anti-drug antibody response and enhances antibacterial efficacy in vivo.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 57 citations in OpenAlex.
- Eradication of MRSA biofilm-associated implant infections by low-immunogenic sustained-release lysostaphin fused to thermosensitive polypeptides.Nature communications · 2026Article
- Bacteriophage Lysins as Programmable Antimicrobials: Mechanisms, Engineering, and Translational Advances.Probiotics and antimicrobial proteins · 2026Review
- A chimeric, half-life extended lysin with a unique mode of action.Frontiers in microbiology · 2026Article
- Phage and Endolysin Therapy Against Antibiotics Resistant Bacteria: From Bench to Bedside.MedComm · 2025Review
- Endolysins: targetingFrontiers in microbiology · 2025Review
- Deleterious Effects of Histidine Tagging to the SH3b Cell Wall-Binding Domain on Recombinant Endolysin Activity.Journal of microbiology and biotechnology · 2024Article
- Agents Targeting the Bacterial Cell Wall as Tools to Combat Gram-Positive Pathogens.Molecules (Basel, Switzerland) · 2024Review
- Machine learning for functional protein design.Nature biotechnology · 2024Review
- Functional Deimmunization of Botulinum Neurotoxin Protease Domain via Computationally Driven Library Design and Ultrahigh-Throughput Screening.ACS synthetic biology · 2023Article
- Immunogenic epitope scanning in bacteriolytic enzymes Pal and Cpl-1 and engineering Pal to escape antibody responses.Frontiers in immunology · 2023Article
- Review
- Biomaterial-based delivery of antimicrobial therapies for the treatment of bacterial infections.Nature reviews. Materials · 2022Article
- Electrostatic-Mediated Affinity Tuning of Lysostaphin Accelerates Bacterial Lysis Kinetics and EnhancesAntimicrobial agents and chemotherapy · 2021Article
- Deimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-ResistantAntimicrobial agents and chemotherapy · 2021Article
- Strategies for Dodging the Obstacles in CAR T Cell Therapy.Frontiers in oncology · 2021Review
- Deimmunization of protein therapeutics - Recent advances in experimental and computational epitope prediction and deletion.Computational and structural biotechnology journal · 2021Review
- Globally deimmunized lysostaphin evades human immune surveillance and enables highly efficacious repeat dosing.Science advances · 2020Article
- A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy.Nature biotechnology · 2020Article
- Linker Editing of Pneumococcal Lysin ClyJ Conveys Improved Bactericidal Activity.Antimicrobial agents and chemotherapy · 2020Article
- Two-site recognition of Staphylococcus aureus peptidoglycan by lysostaphin SH3b.Nature chemical biology · 2020Article
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 at 1 institution in 2 countries.
Funding
Abstract
The enzyme lysostaphin possesses potent anti-staphylococcal activity and represents a promising antibacterial drug candidate; however, its immunogenicity poses a barrier to clinical translation. Here, structure-based biomolecular design enabled widespread depletion of lysostaphin DRB1(∗)0401 restricted T cell epitopes, and resulting deimmunized variants exhibited striking reductions in anti-drug antibody responses upon administration to humanized HLA-transgenic mice. This reduced immunogenicity translated into improved efficacy in the form of protection against repeated challenges with methicillin-resistant Staphylococcus aureus (MRSA). In contrast, while wild-type lysostaphin was efficacious against the initial MRSA infection, it failed to clear subsequent bacterial challenges that were coincident with escalating anti-drug antibody titers. These results extend the existing deimmunization literature, in which reduced immunogenicity and retained efficacy are assessed independently of each other. By correlating in vivo efficacy with longitudinal measures of anti-drug antibody development, we provide the first direct evidence that T cell epitope depletion manifests enhanced biotherapeutic efficacy.
Indexed as
Identifiers
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.