Creation of Polyvalent Decoys of Protein Cytotoxins as Therapeutics and Vaccines
Abstract
Polyvalent protein shells (capsids) are useful platforms for the display of molecules of interest (MOI) on their surface. The resulting polyvalent reagents act as efficacious prophylactic vaccines and therapeutics. The coat protein subunits of Tomato Bushy Stunt Virus (TBSV) and structurally similar Norwalk viruses, when expressed in insect cells, spontaneously self assemble to form protein shells. The self-assembly of the coat protein mutants of TBSV resulted in two types of nanoparticles: small (60 subunit) and the regular size (180 subunit) capsids. These protein shells (capsids) can be used for the display of 60-180 copies of peptides/proteins of the pathogens of concern. Previously, it has been shown that antibodies raised against various cytotoxins (e.g., ricin and Shiga toxin) render protection against the potential toxin attack. The proposed polyvalent reagents, which display various peptide/protein fragments of ricin would act as prophylactic vaccines of the ricin toxin. As a proof of concept we have successfully generated a reagent displaying one of the ricin peptides (RTA, 95-110) on the surface of TBSV. Generation of other reagents and estimation of their efficacy are underway. Continued support is requested for the creation of new and novel reagents that render protection against the different types of cytotoxins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2005
- Accession Number
- ADA442464
Entities
People
- Vijay S. Reddy
Organizations
- Scripps Research