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Updated: Aug 6, 2026

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Published on: November 16, 2016

A fully human streptolysin O-neutralizing monoclonal antibody improves survival in a murine model of group A

Emily Price1, Anyauba Nmaju1,2, Sabrina Faozia1,3

  • 1Boise VA Medical Center, Boise, Idaho, USA.

Antimicrobial Agents and Chemotherapy
|July 17, 2026
PubMed

Insights

New monoclonal antibodies targeting Streptolysin O (SLO) show promise for treating necrotizing soft tissue infections (NSTIs). One antibody, L17, significantly improved outcomes in a mouse model of group A streptococcus (GAS) infection.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Necrotizing soft tissue infections (NSTIs) caused by Streptococcus pyogenes (group A streptococcus, GAS) are severe, toxin-mediated diseases.
  • Streptolysin O (SLO) is a critical toxin in GAS pathogenesis, contributing to tissue damage and immune suppression.
  • Currently, no targeted antitoxin therapies exist for GAS-driven NSTIs.

Purpose of the Study:

  • To isolate and characterize human monoclonal antibodies (huMAbs) against SLO.
  • To evaluate the therapeutic potential of these huMAbs in preclinical models of GAS-NSTI.

Main Methods:

  • Isolation of SLO-specific memory B cells from a naturally immunized donor.
  • Characterization of three fully human monoclonal antibodies (huMAbs): C11, G4, and L17.
  • In vitro assessment of SLO neutralization and hemolysis inhibition.
  • In vivo efficacy evaluation in a murine model of GAS-NSTI.

Main Results:

  • All three huMAbs (C11, G4, L17) demonstrated high-affinity binding to SLO and potent in vitro neutralization of SLO-induced hemolysis.
  • Antibodies C11 and G4 inhibited SLO membrane binding, while L17 protected cells without blocking binding.
  • Only L17 significantly improved disease outcomes in vivo, reducing clinical severity and prolonging survival by ~130% in a murine GAS-NSTI model.

Conclusions:

  • Antibody-mediated neutralization of SLO can effectively alter disease progression in GAS-necrotizing infections.
  • The huMAb L17 shows significant therapeutic potential as an antitoxin for treating GAS-NSTI.
Keywords:
Streptococcus pyogenesmonoclonal antibodiesnecrotizing soft tissue infectionsstreptolysin Otoxin neutralization

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