ArticleScientific reports2019
Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing monoclonal IgGs penetrating the epithelial lining fluid.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Acidic and alkaline conditions enhance Staphylococcus aureus α-toxin pore formation and cytotoxicity.PLoS pathogens · 2026Article
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Human anti-alpha-hemolysin scFvs mitigate toxin-mediated damage in a mouse model of MRSA pneumonia.Applied microbiology and biotechnology · 2026Article
- Review
- A SpA+LukAB vaccine targeting Staphylococcus aureus evasion factors restricts infection in two minipig infection models.NPJ vaccines · 2025Article
- Forssman and the staphylococcal hemolysins.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2025Review
- Complex Regulation of Gamma-Hemolysin Expression Impacts Staphylococcus aureus Virulence.Microbiology spectrum · 2023Article
- Neutralization of Staphylococcus aureus Protein A Prevents Exacerbated Osteoclast Activity and Bone Loss during Osteomyelitis.Antimicrobial agents and chemotherapy · 2023Article
- In Vivo Pathogenicity of Methicillin-SusceptibleLife (Basel, Switzerland) · 2022Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Pathogenicity and virulence ofVirulence · 2021Review
- Development of Combination Vaccine Conferring Optimal Protection against Six Pore-Forming Toxins of Staphylococcus aureus.Infection and immunity · 2021Article
- Review
- Staphylococcal Infections: Host and Pathogenic Factors.Microorganisms · 2021Article
- Monoclonal Antibodies Targeting Surface-Exposed and Secreted Proteins from Staphylococci.Vaccines · 2021Review
- Review
- Review
- Review
- Antivirulence Strategies for the Treatment ofFrontiers in microbiology · 2020Review
- Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia.Infection and immunity · 2019Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Staphylococcus aureus pneumonia is associated with high mortality irrespective of antibiotic susceptibility. Both MRSA and MSSA strains produce powerful cytotoxins: alpha-hemolysin(Hla) and up to five leukocidins - LukSF-PV, HlgAB, HlgCB, LukED and LukGH (LukAB) - to evade host innate defense mechanisms. Neutralizing cytotoxins has been shown to provide survival benefit in rabbit S. aureus pneumonia models. We studied the mechanisms of protection of ASN100, a combination of two human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize Hla and the five leukocidins, in rabbit MRSA and MSSA pneumonia models. Upon prophylactic passive immunization, ASN100 displayed dose-dependent increase in survival and was fully protective against all S. aureus strains tested at 5 or 20 mg/kg doses. Macroscopic and microscopic lung pathology, edema rate, and bacterial burden were evaluated 12 hours post infection and reduced by ASN100. Pharmacokinetic analysis of ASN100 in bronchoalveolar-lavage fluid from uninfected animals detected efficient penetration to lung epithelial lining fluid reaching peak levels between 24 and 48 hours post dosing that were comparable to the mAb concentration measured in serum. These data confirm that the ASN100 mAbs neutralize the powerful cytotoxins of S. aureus in the lung and prevent damage to the mucosal barrier and innate immune cells.
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