ArticleClinical and vaccine immunology : CVI2012
Identification of anti-alpha toxin monoclonal antibodies that reduce the severity of Staphylococcus aureus dermonecrosis and exhibit a correlation between affinity and potency.
Article in Clinical and vaccine immunology : CVI, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed.
- Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults.Antimicrobial agents and chemotherapy · 2017Trial
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- Novel Therapies for Prosthetic Joint Infections Caused by Methicillin-ResistantPathogens (Basel, Switzerland) · 2025Review
- citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform.Nature communications · 2025Article
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- YjbH contributes toVirulence · 2024Article
- Enhanced Staphylococcus aureus protection by uncoupling of the α-toxin-ADAM10 interaction during murine neonatal vaccination.Nature communications · 2024Article
- In vivo mRNA expression of a multi-mechanistic mAb combination protects against Staphylococcus aureus infection.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.The Journal of pharmacology and experimental therapeutics · 2024Review
- Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes ofJournal of Korean medical science · 2023Article
- Monoclonal antibodies neutralizing alpha-hemolysin, bicomponent leukocidins, and clumping factor A protected againstFrontiers in immunology · 2023Article
- Monoclonal antibody therapeutics for infectious diseases: Beyond normal human immunoglobulin.Pharmacology & therapeutics · 2022Review
- Quinones as an Efficient Molecular Scaffold in the Antibacterial/Antifungal or Antitumoral Arsenal.International journal of molecular sciences · 2022Review
- Identification of two neutralizing human single-chain variable fragment antibodies targetingIranian journal of basic medical sciences · 2022Article
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- A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.PLoS pathogens · 2022Article
- Production of an Antibody Fragment (scFv) Targeting PcrV Protein of Pseudomonas aeruginosa in Fed-Batch Cultivation ModeIranian biomedical journal · 2021Article
- Mutations in a Membrane Permease orAntimicrobial agents and chemotherapy · 2021Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staphylococcus aureus alpha toxin (AT) is an important virulence determinant and may be a valid target for immunoprophylaxis against staphylococcal disease. Here we report the identification of potent inhibitory anti-AT monoclonal antibodies (MAbs) derived using B-cell hybridoma technology from VelocImmune mice engineered to produce IgG with a human variable domain. A small panel of inhibitory MAbs blocked AT-mediated lysis of rabbit red blood cells, A549 human lung epithelial cells, and THP-1 human monocytic cells, in a dose-dependent manner. Binding studies indicated that these MAbs recognize a similar epitope on AT and exhibit dissociation constants (K(D)) ranging from 0.50 to 15 nM. In an S. aureus dermonecrosis model, mice passively immunized with anti-AT inhibitory MAbs exhibited significant reductions of lesion size relative to mice treated with an irrelevant IgG control. Interestingly, there was a correlation between MAb affinity for a single epitope, the 50% inhibitory concentration (IC(50)) in the AT hemolytic assay, and lesion size reduction in the dermonecrosis model. A representative high-affinity MAb, 2A3.1, was demonstrated to significantly reduce lesion size following infection with three different clinical isolates (USA300, CC30, and CC5). Taken together, these results indicate that in vitro potency of anti-AT MAbs predicts in vivo potency in this model, supporting their continued preclinical evaluation as molecules for immunoprophylaxis against staphylococcal skin and soft tissue infections caused by diverse clinical isolates.
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