Citations

3636 total record number
147 records this year

To narrow your search, use one or more of the following search menus below.

To search by keyword, you may search by type of cell/animal/assay/protein/research or publication.

Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB) protective against toxic shock syndrome

Karauzum, H;Chen, G;Abaandou, L;Mahmoudieh, M;Boroun, AR;Shulenin, S;Devi, VS;Stavale, E;Warfield, KL;Zeitlin, L;Roy, CJ;Sidhu, SS;Aman, MJ;
Product: LPS from Escherichia coli O55:B5

Staphylococcal enterotoxin B (SEB) is a potent toxin that can cause toxic shock syndrome and act as a lethal and incapacitating agent when used as a bioweapon. There are currently no vaccines or immunotherapeutics available against this toxin. Using phage display technology, human antigen-binding fragments (Fabs) were selected against SEB, and proteins were produced in Escherichia coli cells and characterized for their binding affinity and their toxin neutralizing activity in vitro and in vivo. Highly protective Fabs were converted into full-length IgGs and produced in mammalian cells. Additionally, the production of anti-SEB antibodies was explored in the Nicotiana benthamiana plant expression system. Affinity maturation was performed to produce optimized lead anti-SEB antibody candidates with subnanomolar affinities. IgGs produced in N. benthamiana showed characteristics comparable with those of counterparts produced in mammalian cells. IgGs were tested for their therapeutic efficacy in the mouse toxic shock model using different challenge doses of SEB and a treatment with 200 μg of IgGs 1 h after SEB challenge. The lead candidates displayed full protection from lethal challenge over a wide range of SEB challenge doses. Furthermore, mice that were treated with anti-SEB IgG had significantly lower IFNγ and IL-2 levels in serum compared with mock-treated mice. In summary, these anti-SEB monoclonal antibodies represent excellent therapeutic candidates for further preclinical and clinical development.

PubMed ID: 22645125
235023502017-06-052017-06-0511:03:0211:03:022018-09-102018-09-1011:29:3911:29:39Karauzum, H;Chen, G;Abaandou, L;Mahmoudieh, M;Boroun, AR;Shulenin, S;Devi, VS;Stavale, E;Warfield, KL;Zeitlin, L;Roy, CJ;Sidhu, SS;Aman, MJ;Karauzum, H;Chen, G;Abaandou, L;Mahmoudieh, M;Boroun, AR;Shulenin, S;Devi, VS;Stavale, E;Warfield, KL;Zeitlin, L;Roy, CJ;Sidhu, SS;Aman, MJ;20122012Synthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB) protective against toxic shock syndromeSynthetic human monoclonal antibodies toward staphylococcal enterotoxin B (SEB) protective against toxic shock syndromeThe Journal Of Biological ChemistryThe Journal Of Biological Chemistry25203-1525203-1528728730302264512522645125

Staphylococcal enterotoxin B (SEB) is a potent toxin that can cause toxic shock syndrome and act as a lethal and incapacitating agent when used as a bioweapon. There are currently no vaccines or immunotherapeutics available against this toxin. Using phage display technology, human antigen-binding fragments (Fabs) were selected against SEB, and proteins were produced in Escherichia coli cells and characterized for their binding affinity and their toxin neutralizing activity in vitro and in vivo. Highly protective Fabs were converted into full-length IgGs and produced in mammalian cells. Additionally, the production of anti-SEB antibodies was explored in the Nicotiana benthamiana plant expression system. Affinity maturation was performed to produce optimized lead anti-SEB antibody candidates with subnanomolar affinities. IgGs produced in N. benthamiana showed characteristics comparable with those of counterparts produced in mammalian cells. IgGs were tested for their therapeutic efficacy in the mouse toxic shock model using different challenge doses of SEB and a treatment with 200 μg of IgGs 1 h after SEB challenge. The lead candidates displayed full protection from lethal challenge over a wide range of SEB challenge doses. Furthermore, mice that were treated with anti-SEB IgG had significantly lower IFNγ and IL-2 levels in serum compared with mock-treated mice. In summary, these anti-SEB monoclonal antibodies represent excellent therapeutic candidates for further preclinical and clinical development.

Staphylococcal enterotoxin B (SEB) is a potent toxin that can cause toxic shock syndrome and act as a lethal and incapacitating agent when used as a bioweapon. There are currently no vaccines or immunotherapeutics available against this toxin. Using phage display technology, human antigen-binding fragments (Fabs) were selected against SEB, and proteins were produced in Escherichia coli cells and characterized for their binding affinity and their toxin neutralizing activity in vitro and in vivo. Highly protective Fabs were converted into full-length IgGs and produced in mammalian cells. Additionally, the production of anti-SEB antibodies was explored in the Nicotiana benthamiana plant expression system. Affinity maturation was performed to produce optimized lead anti-SEB antibody candidates with subnanomolar affinities. IgGs produced in N. benthamiana showed characteristics comparable with those of counterparts produced in mammalian cells. IgGs were tested for their therapeutic efficacy in the mouse toxic shock model using different challenge doses of SEB and a treatment with 200 μg of IgGs 1 h after SEB challenge. The lead candidates displayed full protection from lethal challenge over a wide range of SEB challenge doses. Furthermore, mice that were treated with anti-SEB IgG had significantly lower IFNγ and IL-2 levels in serum compared with mock-treated mice. In summary, these anti-SEB monoclonal antibodies represent excellent therapeutic candidates for further preclinical and clinical development.

4.64.6

Bacterial Superantigens and Endotoxin:

... Lipopolysaccharide (LPS; Escherichia coli 055:B5) was purchased from List Biological Laboratories, Inc. (Campbell, CA) and reconstituted with PBS prior to use. ...

NOTE:  At the time this paper was written, Product #203 (5mg - LPS from Escherichia coli O55:B5) was utilized.

Product #203 (5 mg - LPS from Escherichia coli O55:B5) is no longer sold.

Product #203A (2.5 mg - LPS from Escherichia coli O55:B5) is available for purchase.

Bacterial Superantigens and Endotoxin:

... Lipopolysaccharide (LPS; Escherichia coli 055:B5) was purchased from List Biological Laboratories, Inc. (Campbell, CA) and reconstituted with PBS prior to use. ...

NOTE:  At the time this paper was written, Product #203 (5mg - LPS from Escherichia coli O55:B5) was utilized.

Product #203 (5 mg - LPS from Escherichia coli O55:B5) is no longer sold.

Product #203A (2.5 mg - LPS from Escherichia coli O55:B5) is available for purchase.

http://www.jbc.org/content/287/30/25203.shorthttp://www.jbc.org/content/287/30/25203.short2012-07-202012-07-2010.1074/jbc.M112.36407510.1074/jbc.M112.364075LPS from Escherichia coli O55:B5LPS from Escherichia coli O55:B5sachdev.sidhu@utoronto.casachdev.sidhu@utoronto.caACT;Activity;Affinity;Agent;Analysis;Anti;Antibodies;Antibody;Antigen;Binding;Biological;Clinical;Development;Efficacy;Escherichia coli;Expression;IgG;IL;In vitro;Lethal;Lipopolysaccharide;List;List Biological;LPS;Mammalian;Monoclonal;Mouse;Neutralizing;PAGE;Phage;Potent;Production;Protective;Purity;SDS;SEB;Shock;Synthetic;Tested;Therapeutic;Toxic;Toxin;Treatment;The Journal Of Biological ChemistryACT;Activity;Affinity;Agent;Analysis;Anti;Antibodies;Antibody;Antigen;Binding;Biological;Clinical;Development;Efficacy;Escherichia coli;Expression;IgG;IL;In vitro;Lethal;Lipopolysaccharide;List;List Biological;LPS;Mammalian;Monoclonal;Mouse;Neutralizing;PAGE;Phage;Potent;Production;Protective;Purity;SDS;SEB;Shock;Synthetic;Tested;Therapeutic;Toxic;Toxin;Treatment;The Journal Of Biological Chemistry203A203Asynthetic-human-monoclonal-antibodies-towardsynthetic-human-monoclonal-antibodies-toward