scholarly journals Mechanisms Mediating Enhanced Neutralization Efficacy of Staphylococcal Enterotoxin B by Combinations of Monoclonal Antibodies

2015 ◽  
Vol 290 (11) ◽  
pp. 6715-6730 ◽  
Author(s):  
Kaushik Dutta ◽  
Avanish K. Varshney ◽  
Matthew C. Franklin ◽  
Michael Goger ◽  
Xiaobo Wang ◽  
...  
2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Daniel Verreault ◽  
Jane Ennis ◽  
Kevin Whaley ◽  
Stephanie Z. Killeen ◽  
Hatice Karauzum ◽  
...  

ABSTRACTStaphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface ofStaphylococcus aureusthat is the source for multiple pathologies in humans. 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 with 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 efficacies 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 of body weight) at either 0.5, 2, or 4 h postexposure. Onset of clinical signs and 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 to 48 h postexposure. These results represent the successful therapeuticin vivoprotection by two investigational drugs against SEB in a severe nonhuman primate disease model and punctuate the therapeutic value of monoclonal antibodies when faced with treatment options for SEB-induced toxicity in a postexposure setting.


1992 ◽  
Vol 89 (5) ◽  
pp. 247-254 ◽  
Author(s):  
Joaquín Goyache ◽  
JoséA. Orden ◽  
JoséL. Blanco ◽  
Javier Hernández ◽  
Ana Doménech ◽  
...  

2012 ◽  
Vol 287 (30) ◽  
pp. 25203-25215 ◽  
Author(s):  
Hatice Karauzum ◽  
Gang Chen ◽  
Laura Abaandou ◽  
Mahta Mahmoudieh ◽  
Atefeh R. Boroun ◽  
...  

2016 ◽  
Vol 40 (10) ◽  
pp. 8334-8341 ◽  
Author(s):  
Arun Sharma ◽  
Vepa Kameswara Rao ◽  
Dev Vrat Kamboj ◽  
Ritu Gaur ◽  
Mahabul Shaik ◽  
...  

We report a ferrocene based electrochemical immunosensor for staphylococcal enterotoxin B.


1994 ◽  
Vol 180 (2) ◽  
pp. 615-621 ◽  
Author(s):  
A R Hamad ◽  
A Herman ◽  
P Marrack ◽  
J W Kappler

Four monoclonal antibodies (mAbs) were produced binding to four nonoverlapping epitopes on the superantigen staphylococcal enterotoxin B (SEB). The mAbs were tested for their ability to detect SEB bound to major histocompatibility complex (MHC) class II, to inhibit SEB binding to MHC class II, to inhibit SEB stimulation of T cell hybridomas, to bind to various nonfunctional mutants of SEB, and to capture and present SEB and its mutants to T cells in the absence of MHC class II. We concluded that two mAbs, B344 and B327, bound to epitopes not required for superantigen function, one mAb, 2B33, blocked an MHC interaction site on SEB, and the fourth mAb, B87, blocked the T cell recognition site on SEB. Moreover, two mAbs (B344 and 2B33) were capable of presenting SEB, although much less efficiently than APC, to CD4- but not CD4+ T cell hybridomas. The results confirm the functional domains on SEB originally defined by mutation and show that MHC class II is not always an essential component of the superantigen ligand.


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