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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus

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Preventing lung pathology and mortality in rabbit Staphylococcus aureus pneumonia models with cytotoxin-neutralizing

Lukas Stulik1, Harald Rouha2, Delphine Labrousse3

  • 1Arsanis Biosciences, Vienna, Austria. lukas.stulik@arsanis.com.

Scientific Reports
|March 31, 2019
PubMed

Insights

ASN100, a combination of two monoclonal antibodies, effectively neutralizes Staphylococcus aureus cytotoxins. This treatment significantly improves survival and reduces lung damage in pneumonia models, offering a promising therapeutic strategy.

Area of Science:

  • Infectious Diseases
  • Immunology
  • Pulmonology

Background:

  • Staphylococcus aureus pneumonia presents high mortality, independent of antibiotic resistance.
  • Both MRSA and MSSA strains produce cytotoxins like alpha-hemolysin (Hla) and leukocidins, crucial for immune evasion.
  • Previous studies indicate neutralizing these toxins can improve survival in pneumonia models.

Purpose of the Study:

  • To evaluate the protective efficacy of ASN100, a dual monoclonal antibody therapy, against S. aureus pneumonia in rabbit models.
  • To investigate the mechanism of ASN100's protection by assessing its impact on lung pathology and bacterial burden.
  • To determine the pharmacokinetic profile of ASN100 in lung tissue.

Main Methods:

  • Prophylactic passive immunization with ASN100 in rabbit models of MRSA and MSSA pneumonia.
  • Assessment of survival rates, macroscopic and microscopic lung pathology, edema, and bacterial burden at 12 hours post-infection.
  • Pharmacokinetic analysis of ASN100 in bronchoalveolar-lavage fluid and serum.

Main Results:

  • ASN100 demonstrated dose-dependent increases in survival and provided full protection at 5 or 20 mg/kg against all tested S. aureus strains.
  • Treatment with ASN100 significantly reduced lung pathology, edema, and bacterial burden.
  • Efficient penetration of ASN100 into lung epithelial lining fluid was observed, with peak concentrations comparable to serum levels.

Conclusions:

  • ASN100 effectively neutralizes key S. aureus cytotoxins in the lung.
  • The antibody combination prevents damage to the mucosal barrier and innate immune cells, improving outcomes in pneumonia.
  • ASN100 represents a potential therapeutic strategy for S. aureus pneumonia by targeting virulence factors.

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