A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy

Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0059823. doi: 10.1128/aac.00598-23. Epub 2023 Dec 4.

Abstract

Shiga toxin-producing Escherichia coli infections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxins, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremic syndrome (HUS). Here, we introduce a potentially therapeutic humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity in healthy adults ex vivo and high neutralizing efficacy in vivo, protecting mice from mortality and HUS-related tissue damage.

Keywords: Shiga toxins; antibacterial therapeutics; experimental therapeutics; monoclonal antibodies.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Escherichia coli Infections* / drug therapy
  • Hemolytic-Uremic Syndrome* / drug therapy
  • Humans
  • Mice
  • Shiga Toxin / therapeutic use
  • Shiga Toxin 2
  • Shiga-Toxigenic Escherichia coli*

Substances

  • Shiga Toxin
  • Shiga Toxin 2
  • Antibodies, Monoclonal, Humanized