Creation and Over-Expression of Polyvalent Capsids Displaying Larger Segments of Ricin Achain as the Efficacious Vaccines of Ricin Toxin
Annual rept. 15 Jul 2005-14 Jul 2006
SCRIPPS RESEARCH INST LA JOLLA CA
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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 StuntVirus 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 peptidesproteins 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 peptideprotein fragments of ricin would act as 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. These reagents when injected into mice generated antibodies, which readily detect the ricin toxin in the western-blot analysis. Hence, these reagents can be used as potential vaccines of the ricin toxin.