A tripartite cocktail of chimeric monoclonal antibodies passively protects mice against ricin, staphylococcal enterotoxin B and Clostridium perfringens epsilon toxin.

Due to the fast-acting nature of ricin, staphylococcal enterotoxin B (SEB), and Clostridium perfringens epsilon toxin (ETX), it is necessary that therapeutic interventions following a bioterrorism incident by one of these toxins occur as soon as possible after intoxication. Moreover, because the clinical manifestations of intoxication by these agents are likely to be indistinguishable from each other, especially following aerosol exposure, we have developed a cocktail of chimeric monoclonal antibodies that is capable of neutralizing all three toxins. The efficacy of this cocktail was demonstrated in mouse models of lethal dose toxin challenge.

[1]  Janice M Reichert,et al.  Monoclonal antibody successes in the clinic , 2005, Nature Biotechnology.

[2]  L. Zeitlin,et al.  Synthetic Human Monoclonal Antibodies toward Staphylococcal Enterotoxin B (SEB) Protective against Toxic Shock Syndrome* , 2012, The Journal of Biological Chemistry.

[3]  M. P. Griffin,et al.  A Novel Investigational Fc-Modified Humanized Monoclonal Antibody, Motavizumab-YTE, Has an Extended Half-Life in Healthy Adults , 2013, Antimicrobial Agents and Chemotherapy.

[4]  O. Bohorov,et al.  Prevention and treatment of Clostridium perfringens epsilon toxin intoxication in mice with a neutralizing monoclonal antibody (c4D7) produced in Nicotiana benthamiana. , 2014, Toxicon : official journal of the International Society on Toxinology.

[5]  G. Stiegler,et al.  Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. , 2008, Plant biotechnology journal.

[6]  N. Mantis Vaccines against the category B toxins: Staphylococcal enterotoxin B, epsilon toxin and ricin. , 2005, Advanced drug delivery reviews.

[7]  N. Mantis,et al.  Resolution of two overlapping neutralizing B cell epitopes within a solvent exposed, immunodominant α-helix in ricin toxin's enzymatic subunit. , 2012, Toxicon : official journal of the International Society on Toxinology.

[8]  N. Mantis,et al.  Comparative Efficacy of Two Leading Candidate Ricin Toxin A Subunit Vaccines in Mice , 2013, Clinical and Vaccine Immunology.

[9]  M. Pauly,et al.  Monoclonal antibodies from plants: A new speed record , 2006, Proceedings of the National Academy of Sciences.

[10]  V. Coljee,et al.  Back to the future: recombinant polyclonal antibody therapeutics , 2013, Current Opinion in Chemical Engineering.

[11]  Ernie Hiatt,et al.  Chimeric Plantibody Passively Protects Mice against Aerosolized Ricin Challenge , 2014, Clinical and Vaccine Immunology.

[12]  H. Barth,et al.  Clostridium perfringens Epsilon Toxin: A Malevolent Molecule for Animals and Man? , 2013, Toxins.

[13]  T. Krakauer,et al.  The staphylococcal enterotoxin (SE) family , 2013, Virulence.

[14]  Carola Engler,et al.  Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors , 2006, Proceedings of the National Academy of Sciences.

[15]  W. Baze,et al.  Aerosolized Staphylococcal Enterotoxin B-Induced Pulmonary Lesions in Rhesus Monkeys (Macaca mulatta) , 1995, Toxicologic pathology.

[16]  G. A. Lazar,et al.  Enhanced antibody half-life improves in vivo activity , 2010, Nature Biotechnology.

[17]  N. Mantis,et al.  Mucosal Vaccines for Biodefense , 2011, Current topics in microbiology and immunology.

[18]  B. Stiles,et al.  Antibodies for biodefense , 2011, mAbs.

[19]  Francisco A Uzal,et al.  Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease. , 2014, Future microbiology.

[20]  P. Hauer,et al.  Development of monoclonal antibodies suitable for use in antigen quantification potency tests for clostridial veterinary vaccines. , 1999, Developments in biological standardization.

[21]  B. McClane,et al.  Evidence for a Prepore Stage in the Action of Clostridium perfringens Epsilon Toxin , 2011, PloS one.

[22]  Daniel N Wolfe,et al.  Current biodefense vaccine programs and challenges , 2013, Human vaccines & immunotherapeutics.

[23]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[24]  C. Lindsay,et al.  Addressing bioterrorism concerns , 2013, Human & experimental toxicology.