scholarly journals Oral administration of recombinant Bacillus subtilis spores expressing mutant staphylococcal enterotoxin B provides potent protection against lethal enterotoxin challenge

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhile Xiong ◽  
Jialiang Mai ◽  
Fei Li ◽  
Bingshao Liang ◽  
Shuwen Yao ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Oral Administration ◽  
Protective Efficacy ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Mutant Form ◽  
Humoral Immune ◽  
Enterotoxin B ◽  
Recombinant Bacillus Subtilis ◽  
Factor Α

AbstractPathogenicity of Staphylococcus aureus is induced by staphylococcal enterotoxin B (SEB). A mutant form of SEB (mSEB) is immunogenic as well as less toxic. Recombinant mSEB and SEB were expressed in pET28a prokaryotic plasmids. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mSEB-stimulated macrophages were lower than those in SEB-stimulated macrophages (p < 0.001, p < 0.01 respectively). Using CotC as a fusion protein, we constructed recombinant Bacillus subtilis spores expressing mSEB on the spore surface and evaluated their safety and protective efficacy via mouse models. Oral administration of mSEB-expressing spores increased SEB-specific IgA in feces and SEB-specific IgG1 and IgG2a in the sera, compared with mice in naïve and CotC spore-treated groups (p < 0.001, p < 0.01, p < 0.001 respectively). Six weeks following oral dosing of recombinant spores, significant differences were not found in the serum biochemical indices between the mSEB group and the naïve and CotC groups. Furthermore, oral administration of mSEB spores increased the survival rate by 33.3% in mice intraperitoneally injected with 5 µg of wild-type SEB plus 25 µg lipopolysaccharide (LPS). In summation, recombinant spores stably expressing mSEB were developed, and oral administration of such recombinant spores induced a humoral immune response and provided protection against SEB challenge in mice.

scholarly journals Oral administration of recombinant Bacillus subtilis spores expressing mutant staphylococcal enterotoxin B provides potent protection against lethal enterotoxin challenge

2020 ◽  
Author(s):  
Zhile Xiong ◽  
Jialiang Mai ◽  
Fei Li ◽  
Bingshao Liang ◽  
Shuwen Yao ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Oral Administration ◽  
Protective Efficacy ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Mutant Form ◽  
Humoral Immune ◽  
Enterotoxin B ◽  
Recombinant Bacillus Subtilis ◽  
Factor Α

Abstract Pathogenicity of Staphylococcus aureus is induced by staphylococcal enterotoxin B (SEB). A mutant form of SEB (mSEB) is immunogenic as well as less toxic. Recombinant mSEB and SEB were expressed in pET28a prokaryotic plasmids. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mSEB-stimulated macrophages were lower than those in SEB-stimulated macrophages (p < 0.01). Using CotC as a fusion protein, we constructed recombinant Bacillus subtilis spores expressing mSEB on the spore surface and evaluated their safety and protective efficacy via mouse models. Oral administration of mSEB-expressing spores increased SEB-specific IgA in feces and SEB-specific IgG1 and IgG2a in the sera, compared with mice in naïve and CotC spore-treated groups (p < 0.001). Six weeks following oral dosing of recombinant spores, significant differences were not found in the serum biochemical indices between the mSEB group and the naïve and CotC groups. Furthermore, oral administration of mSEB spores increased the survival rate by 33.3% in mice intraperitoneally injected with 5 μg of wild-type SEB plus 25 μg lipopolysaccharide (LPS). In summation, recombinant spores stably expressing mSEB were developed, and oral administration of such recombinant spores induced a humoral immune response and provided protection against SEB challenge in mice.

Staphylococcal enterotoxin B potentiates LPS-induced hepatic dysfunction in chronically catheterized rats

2001 ◽  
Vol 280 (5) ◽  
pp. G866-G872 ◽  
Author(s):  
David W. A. Beno ◽  
Michael R. Uhing ◽  
Masakatsu Goto ◽  
Yong Chen ◽  
Vanida A. Jiyamapa-Serna ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Hepatic Dysfunction ◽  
Hepatic Function ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Physiol Gastrointest Liver ◽  
Enterotoxin B ◽  
Factor Α ◽  
Necrosis Factor

Most models of liver dysfunction in sepsis use endotoxin (lipopolysaccharide; LPS) to induce a pathophysiological response. In our study published in this issue (Beno DWA, Uhing MR, Goto M, Chen Y, Jiyamapa-Serna VA, and Kimura RE. Am J Physiol Gastrointest Liver Physiol 280: G858–G865, 2001), the adverse effect of LPS on hepatic function in vivo was only significant at relatively high LPS doses despite high tumor necrosis factor-α concentrations. However, many patients with sepsis are exposed to multiple bacterial toxins that may augment the immune response, resulting in increased hepatic dysfunction. We have developed a model of polymicrobial sepsis by parentally administering a combination of staphylococcal enterotoxin B (SEB) and LPS. Using this model, we demonstrate that SEB (50 μg/kg) potentiates the effect of LPS-induced hepatic dysfunction as measured by decreased rates of biliary indocyanine green clearance and bile flow. These increases were most pronounced with doses of 10 and 100 μg/kg LPS, doses that by themselves do not induce hepatic dysfunction. This may explain the seemingly increased incidence and severity of liver dysfunction in sepsis, and it suggests that the exclusive use of LPS for replicating septic shock may not be relevant for studies of hepatic dysfunction.

scholarly journals Isotype Switching Increases Efficacy of Antibody Protection against Staphylococcal Enterotoxin B-Induced Lethal Shock and Staphylococcus aureus Sepsis in Mice

mBio ◽  
2014 ◽  
Vol 5 (3) ◽  
Author(s):  
Avanish K. Varshney ◽  
Xiaobo Wang ◽  
Jorge L. Aguilar ◽  
Matthew D. Scharff ◽  
Bettina C. Fries
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibody ◽  
Protective Efficacy ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Antigen Specificity ◽  
Content Type ◽  
Lethal Shock ◽  
Enterotoxin B

ABSTRACTStaphylococcal enterotoxin B (SEB) is a potent toxin that is produced byStaphylococcus aureusstrains and is classified as a category B select agent. We have previously shown that monoclonal antibody (MAb) 20B1, a murine anti-SEB IgG1, successfully treats SEB-induced lethal shock (SEBILS) and bacteremia that is caused by SEB-producingS. aureus. In this study, we have generated two isotype switch variants of the original IgG1 MAb 20B1, an IgG2a and IgG2b, both bearing the same variable region sequence, and compared their neutralizing and protective activity inin vitroandin vivoassays, respectively. All 3 isotypes demonstrated comparable affinity to SEB and comparable 50% inhibitory concentrations (IC50s) in T cell proliferation assays.In vivo, however, the IgG2a isotype variant of 20B1 exhibited significantly greater protection than IgG1 or IgG2b in murine SEB intoxication andS. aureussepsis models. Protection was associated with downmodulation of inflammatory host response. Our data demonstrate that changing the isotype of already protective MAbs, without affecting their antigen specificity or sensitivity, can result in an enhancement of their protective ability. Isotype selection, therefore, should be carefully considered in the development of toxin-neutralizing MAbs and the design of antibody therapeutics.IMPORTANCEThe purpose of this study was to enhance the protective efficacy of an existing, protective monoclonal antibody against staphylococcal enterotoxin B. Using twoin vivomouse models, our study demonstrates that the protective efficacy of a monoclonal antibody may be improved by inducing an isotype switch at the Fc region of an antibody, without altering the antigen specificity or sensitivity of the antibody. The development of therapeutic MAbs with higher efficacy may allow for the achievement of equal therapeutic benefit with a lower dosage. In turn, the use of lower doses may reduce the cost of these therapies, while reducing the potential for adverse side effects.

scholarly journals Therapeutic Treatment of Aerosolized Staphylococcal Enterotoxin B in Nonhuman Primates with two Monoclonal Antibodies

2018 ◽  
Author(s):  
Daniel Verreault ◽  
Jane Ennis ◽  
Kevin Whaley ◽  
Stephanie Z. Killeen ◽  
Hatice Karauzum ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Nonhuman Primate ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Clinical Signs ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Primate Model ◽  
Enterotoxin B

AbstractStaphylococcal enterotoxin B (SEB) is a protein exotoxin found on the cell surface ofStaphylococcus aureusthat 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 therapeuticin vivoprotection 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

scholarly journals Rapid and simultaneous detection of ricin, staphylococcal enterotoxin B and saxitoxin by chemiluminescence-based microarray immunoassay

The Analyst ◽  
2014 ◽  
Vol 139 (22) ◽  
pp. 5885-5892 ◽  
Author(s):  
A. Szkola ◽  
E. M. Linares ◽  
S. Worbs ◽  
B. G. Dorner ◽  
R. Dietrich ◽  
...  
Keyword(s):  
Simultaneous Detection ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Microarray Immunoassay ◽  
Enterotoxin B ◽  
Idiotypic Antibody

Simultaneous detection of proteotoxins, ricin and SEB, and small toxin, STX, on a chemiluminescence-based microarray using anti-idiotypic antibody for STX.

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