A novel composite immunotoxin that suppresses rabies virus production by the infected cells.
Using strepavidin as a scaffold, we have assembled a composite immunotoxin that consists of recombinant Pseudomonas exotoxin A subunit (PE38) and recombinant 25-D1.16 Fab fragment which recognizes the SIINFEKL (pOV8) peptide from ovalbumin in association with H-2K(b) MHC class I protein. The composite immunotoxin exercises cytotoxicity against H-2K(b+) cells sensitized with pOV8 peptide but not with irrelevant peptide. Specific binding of the immunotoxin to H-2K(b+) cells infected with recombinant rabies virus (RV) expressing pOV8 epitope (RV-pOV8) resulted in the suppression of the production of virus particles by the infected cells. This strategy allows readily produce different immunotoxins with desired specificity by combining various targeting and toxin molecules. The results provide a proof of concept that composite immunotoxins can be utilized as novel immunotherapeutics to stop virus spread in the acute phase of the infection allowing winning time for the development of protective immune response.
Mareeva
Tatiana
T
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
Wanjalla
Celestine
C
Schnell
Matthias J
MJ
Sykulev
Yuri
Y
D036002:ADP Ribose Transferases / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D017951:Antigen Presentation; D000998:Antiviral Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D002460:Cell Line; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D000939:Epitopes; D005098:Exotoxins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D000922:Immunotoxins / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011820:Rabies virus / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014771:Virion / Q000187:drug effects; D037521:Virulence Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000998:Antiviral Agents; D001427:Bacterial Toxins; D000939:Epitopes; D005098:Exotoxins; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D010047:Ovalbumin; D010446:Peptide Fragments; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C110366:OVA-8