Noninvasive optical and nuclear imaging of Staphylococcus-specific infection with a human monoclonal antibody-based probe

Francisco Romero Pastrana, John M. Thompson, Marjolein Heuker, Hedzer Hoekstra, Carly A. Dillen, Roger V. Ortines, Alyssa G. Ashbaugh, Julie E. Pickett, Matthijs D. Linssen, Nicholas M. Bernthal, Kevin P. Francis, Girbe Buist, Marleen van Oosten, Gooitzen M. van Dam, Daniel L. J. Thorek, Lloyd S. Miller, Jan Maarten van Dijl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)
283 Downloads (Pure)

Abstract

Staphylococcus aureus infections are a major threat in healthcare, requiring adequate early-stage diagnosis and treatment. This calls for novel diagnostic tools that allow noninvasive in vivo detection of staphylococci. Here we performed a preclinical study to investigate a novel fully-human monoclonal antibody 1D9 that specifically targets the immunodominant staphylococcal antigen A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further target other staphylococcal species. Importantly, using a human post-mortem implant model and an in vivo murine skin infection model, preclinical feasibility was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to be applied for direct optical imaging of in vivo S. aureus infections. Additionally, (89)Zirconium-labeled 1D9 could be used for positron emission tomography imaging of an in vivo S. aureus thigh infection model. Our findings pave the way towards clinical implementation of targeted imaging of staphylococcal infections using the human monoclonal antibody

Original languageEnglish
Pages (from-to)262-272
Number of pages11
JournalVirulence
Volume9
Issue number1
DOIs
Publication statusPublished - Jan-2018

Keywords

  • human monoclonal antibody
  • immunodominant staphylococcal antigen A
  • IsaA
  • PET
  • Zr-89
  • Staphylococcus aureus
  • BACTERIAL-INFECTIONS
  • IN-VIVO
  • AUREUS INFECTIONS
  • TUBERCULOSIS
  • ACTIVATION
  • MECHANISMS
  • RESISTANCE
  • DETECT
  • MICE
  • ISAA

Cite this