Abstract
Staphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface of Staphylococcus aureus that is the source for multiple pathologies in man. When purified and concentrated in aerosol form, SEB can cause an acute and often fatal intoxication, and thus is considered a biological threat agent. There are currently no vaccines or treatments approved for human use. Studies in rodent models of SEB intoxication show that antibody therapy may be a promising treatment strategy, however many have used antibodies only prophylactically or well before any clinical signs of intoxication are apparent. We assessed and compared the protective efficacy of two monoclonal antibodies, Ig121 and c19F1, when administered after aerosol exposure in a uniformly lethal nonhuman primate model of SEB intoxication. Rhesus macaques were challenged using small particle aerosols of SEB, and then were infused intravenously with a single dose of either Ig121 or c19F1 (10 mg/kg) at either 0.5, 2 or 4 hours postexposure. Onset of clinical signs, hematological, and cytokine response in untreated controls confirmed the acute onset and potency of the toxin used in the challenge. All animals administered either Ig121 or c19F1 survived SEB challenge, whereas the untreated controls succumbed to SEB intoxication 30-48 hours postexposure. These results represent the successful therapeutic in vivo protection by two investigational drugs against SEB in a severe nonhuman primate disease model and punctuate the therapeutic value of monoclonal antibodies hold when faced with treatment options for SEB-induced toxicity in a postexposure setting.
One Sentence Summary: Two high-affinity monoclonal antibodies were tested for therapeutic efficacy using a rhesus macaque challenge model of aerosolized SEB
Abbreviations used
- ALT
- alanine aminotransferase
- APCs
- antigen presenting cells
- AST
- aspartate aminotransferase
- AAALAC
- Association for the Assessment and Accreditation of Laboratory Animal Care International
- BUN
- blood urea nitrogen
- CDC
- Centers for Disease Prevention and Control
- ED50
- effective dose 50%
- ELISA
- enzyme linked immunosorbent assay
- G-CSF
- granulocyte colony-stimulating factor
- GM-CSF
- granulocyte macrophage colony stimulating factor
- HRP
- horseradish perioxidase
- IL-18
- interleukin 18
- IL-17
- interleukin 17
- IL-15
- interleukin 15
- IL-13
- interleukin 13
- IL-12/23
- interleukin12/23
- IL-10
- interleukin 10
- IL-8
- interleukin 8
- IL-6
- interleukin 6
- IL-5
- interleukin 5
- IL-4
- interleukin 4
- IL-2
- interleukin 2
- IL-1β
- interleukin 1 beta
- IL-1ra
- interleukin 1 receptor antagonist
- IM
- intramuscular
- IV
- intravenous
- IFN-γ
- interferon gamma
- LD50
- lethal dose 50%
- LPS
- lipopolysaccharide
- MHC
- major histocompatibility complex
- MIP-1β
- macrophage inflammatory protein-1 beta
- MIP-1α
- macrophage inflammatory protein-1 alpha
- MCP-1
- monocyte chemoattractant protein-1
- NIH
- National Institutes of Health
- SIV
- simian immunodeficiency virus
- sCD40L
- soluble CD40-ligand
- SEB
- staphylococcal enterotoxin B
- SAgs
- superantigens
- TCR
- T cell receptor
- TSS
- toxic shock syndrome
- TMB
- 3,3’,5,5’-Tetramethylbenzidine
- TNPRC
- Tulane National Primate Research Center
- TNF-α
- tumor necrosis factor-alpha
- TGF-α
- tumor granulocyte factor-alpha
- VEGF
- vascular endothelial growth factor
Abbreviations used
- ALT
- alanine aminotransferase
- APCs
- antigen presenting cells
- AST
- aspartate aminotransferase
- AAALAC
- Association for the Assessment and Accreditation of Laboratory Animal Care International
- BUN
- blood urea nitrogen
- CDC
- Centers for Disease Prevention and Control
- ED50
- effective dose 50%
- ELISA
- enzyme linked immunosorbent assay
- G-CSF
- granulocyte colony-stimulating factor
- GM-CSF
- granulocyte macrophage colony stimulating factor
- HRP
- horseradish perioxidase
- IL-18
- interleukin 18
- IL-17
- interleukin 17
- IL-15
- interleukin 15
- IL-13
- interleukin 13
- IL-12/23
- interleukin12/23
- IL-10
- interleukin 10
- IL-8
- interleukin 8
- IL-6
- interleukin 6
- IL-5
- interleukin 5
- IL-4
- interleukin 4
- IL-2
- interleukin 2
- IL-1β
- interleukin 1 beta
- IL-1ra
- interleukin 1 receptor antagonist
- IM
- intramuscular
- IV
- intravenous
- IFN-γ
- interferon gamma
- LD50
- lethal dose 50%
- LPS
- lipopolysaccharide
- MHC
- major histocompatibility complex
- MIP-1β
- macrophage inflammatory protein-1 beta
- MIP-1α
- macrophage inflammatory protein-1 alpha
- MCP-1
- monocyte chemoattractant protein-1
- NIH
- National Institutes of Health
- SIV
- simian immunodeficiency virus
- sCD40L
- soluble CD40-ligand
- SEB
- staphylococcal enterotoxin B
- SAgs
- superantigens
- TCR
- T cell receptor
- TSS
- toxic shock syndrome
- TMB
- 3,3’,5,5’-Tetramethylbenzidine
- TNPRC
- Tulane National Primate Research Center
- TNF-α
- tumor necrosis factor-alpha
- TGF-α
- tumor granulocyte factor-alpha
- VEGF
- vascular endothelial growth factor