Creation of Polyvalent Decoys of Protein Cytotoxins as Therapeutics and Vaccines

摘要

Polyvalent protein shells (capsids) are useful platforms for the display of molecules of interest (MOI) on their surface. The resulting polyvalent reagents can be used 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. Norwalk virus particles predominantly result in formation of 180 subunit shells. 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 efficacious prophylactic vaccines of the ricin toxin by priming the immune system. We have successfully produced two polyvalent reagents displaying multiple copies of 1) 16 a.a. RTA antigenic peptide (mouse epitope) and 2) a large 188 a.a. stable RTA domain.