Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design.
Viruses-like particles (VLPs) are frequently being used as platforms for polyvalent display of foreign epitopes of interest on their capsid surface to improve their presentation enhancing the antigenicity and host immune response. In the present study, we used the VLPs of Tomato bushy stunt virus (TBSV), an icosahedral plant virus, as a platform to display 180 copies of 16 amino acid epitopes of ricin toxin fused to the C-terminal end of a modified TBSV capsid protein (NDelta52). Expression of the chimeric recombinant protein in insect cells resulted in spontaneous assembly of VLPs displaying the ricin epitope. Cryo-electron microscopy and image reconstruction of the chimeric VLPs at 22 A resolution revealed the locations and orientation of the ricin epitope exposed on the TBSV capsid surface. Furthermore, injection of chimeric VLPs into mice generated antisera that detected the native ricin toxin. The ease of fusing of short peptides of 15-20 residues and their ability to form two kinds (T=1, T=3) of bio-nanoparticles that result in the display of 60 or 180 copies of less constrained and highly exposed antigenic epitopes makes TBSV an attractive and versatile display platform for vaccine design.
Department of Molecular Biology, TPC-6, The Scripps Research Institute, La Jolla, CA 92037, USA.
Shantanu
S
Kumar
Wendy
W
Ochoa
Pratik
P
Singh
Catherine
C
Hsu
Anette
A
Schneemann
Marianne
M
Manchester
Mark
M
Olson
Vijay
V
Reddy
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000378:metabolism*; D007313:Insecta; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012276:Ricin / Q000276:immunology / Q000378:metabolism; D017864:Tombusvirus / Q000502:physiology*; D014612:Vaccines
D000941:Antigens; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D012276:Ricin