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Updated: Mar 25, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus
Yilong Yang1, Mengying Qian1, Shaoqiong Yi1
1Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, PR China.
Abstract:
Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections.
Insights
A new monoclonal antibody (mAb) targeting Staphylococcus aureus surface protein A (SasA) shows promise for treating methicillin-resistant Staphylococcus aureus (MRSA) infections. This anti-SasA mAb effectively cleared bacteria and improved survival in preclinical models.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) presents a significant public health challenge due to widespread antibiotic resistance.
- Novel therapeutic strategies, including monoclonal antibodies (mAbs), are urgently needed to combat MRSA infections.
- Staphylococcus aureus surface protein A (SasA) is a potential target for immunotherapies against S. aureus.
Purpose of the Study:
- To analyze the SasA protein sequence using bioinformatics.
- To generate a protective monoclonal antibody (mAb) targeting a conserved domain of SasA.
- To evaluate the efficacy of the anti-SasA mAb (2H7) against MRSA infections in preclinical models.
Main Methods:
- Bioinformatic analysis of the SasA protein sequence.
- Generation and characterization of the 2H7 monoclonal antibody.
- In vitro assessment of S. aureus opsonophagocytic killing.
- In vivo evaluation in murine models of sepsis and peritoneal infection using MRSA strains USA300 and ST239.
Main Results:
- The 2H7 mAb recognized wild-type S. aureus and promoted opsonophagocytic killing.
- Prophylactic administration of 2H7 improved survival and enhanced bacterial clearance in kidneys in sepsis and peritoneal infection models.
- 2H7 prophylaxis prevented abscess formation in a peritoneal infection model, and therapeutic administration showed protective effects in a sepsis model.
Conclusions:
- An anti-SasA mAb (2H7) demonstrates significant protective efficacy against MRSA infections in preclinical models.
- Targeting SasA with mAbs represents a promising immunotherapeutic strategy for MRSA infections.
- These findings support the potential of anti-SasA mAbs as a component of antibody-based treatments for MRSA.
