ArticlemAbs2015
Five birds, one stone: neutralization of α-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 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
91 citing papers in PubMed, 142 citations in OpenAlex.
- Randomized, Double-Blind, Placebo-Controlled, Single-Ascending-Dose Study of the Penetration of a Monoclonal Antibody Combination (ASN100) TargetingAntimicrobial agents and chemotherapy · 2019Trial
- Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults.Human vaccines & immunotherapeutics · 2017Trial
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate antiproliferative effects.The Journal of biological chemistry · 2026Article
- Bacterial pore-forming toxins: mechanisms and implications for host immunity.Bioscience reports · 2026Review
- Taming Superbugs: Current Progress and Challenges in Combating ESKAPE Pathogens.Pathogens (Basel, Switzerland) · 2025Review
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate anti-proliferative effects.bioRxiv : the preprint server for biology · 2025Article
- Review
- Forssman and the staphylococcal hemolysins.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2025Review
- Monoclonal antibodies: From magic bullet to precision weapon.Molecular biomedicine · 2024Review
- Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023Review
- Article
- Recent Approaches for Downplaying Antibiotic Resistance: Molecular Mechanisms.BioMed research international · 2023Review
- Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia.Frontiers in cellular and infection microbiology · 2023Article
- Identification of two neutralizing human single-chain variable fragment antibodies targetingIranian journal of basic medical sciences · 2022Article
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.Science (New York, N.Y.) · 2022Article
- Anti-ACVR1 antibodies exacerbate heterotopic ossification in fibrodysplasia ossificans progressiva (FOP) by activating FOP-mutant ACVR1.The Journal of clinical investigation · 2022Article
- Anti-bacterial monoclonal antibodies: next generation therapy against superbugs.Applied microbiology and biotechnology · 2022Review
- Methicillin-Resistant Staphylococcus aureus Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia.Seminars in respiratory and critical care medicine · 2022Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
31 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
25 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staphylococcus aureus is a major human pathogen associated with high mortality. The emergence of antibiotic resistance and the inability of antibiotics to counteract bacterial cytotoxins involved in the pathogenesis of S. aureus call for novel therapeutic approaches, such as passive immunization with monoclonal antibodies (mAbs). The complexity of staphylococcal pathogenesis and past failures with single mAb products represent considerable barriers for antibody-based therapeutics. Over the past few years, efforts have focused on neutralizing α-hemolysin. Recent findings suggest that the concerted actions of several cytotoxins, including the bi-component leukocidins play important roles in staphylococcal pathogenesis. Therefore, we aimed to isolate mAbs that bind to multiple cytolysins by employing high diversity human IgG1 libraries presented on the surface of yeast cells. Here we describe cross-reactive antibodies with picomolar affinity for α-hemolysin and 4 different bi-component leukocidins that share only ∼26% overall amino acid sequence identity. The molecular basis of cross-reactivity is the recognition of a conformational epitope shared by α-hemolysin and F-components of gamma-hemolysin (HlgAB and HlgCB), LukED and LukSF (Panton-Valentine Leukocidin). The amino acids predicted to form the epitope are conserved and known to be important for cytotoxic activity. We found that a single cross-reactive antibody prevented lysis of human phagocytes, epithelial and red blood cells induced by α-hemolysin and leukocidins in vitro, and therefore had superior effectiveness compared to α-hemolysin specific antibodies to protect from the combined cytolytic effect of secreted S. aureus toxins. Such mAb afforded high levels of protection in murine models of pneumonia and sepsis.
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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.