Delivery of a foreign epitope by sharing amino acid residues with the carrier matrix.
A broad range of structural viral proteins has the ability to assemble into virus-like particles (VLPs). Under the condition that modified subunits are still competent to assemble into VLPs, they are epitope delivery platforms suitable for vaccination purposes. The insertion of foreign sequences can be detrimental for the formation of chimeric VLPs as a result of misfolded subunit proteins. Hence, a strategy was adopted to screen for locations allowing the use of shared residues between the wildtype subunit sequence and the foreign insert. The insertion of a cysteine-containing sequence of hepatitis C virus (HCV) envelope protein 2 (E2) without adding an additional cysteine residue retained the ability of recombinant small hepatitis B surface antigen (HBsAg-S) to form secretion competent VLPs. A cysteine residue shared by the insert and the template protein avoided the formation of non-native disulfide bonds, and allowed the formation of VLPs. The chimeric HBsAg-S VLPs were similar to wildtype VLPs in density exposing the inserted foreign epitope and being immunogenic. Overall, the use of shared sequences between the insert and the subunit will facilitate the design of chimeric VLPs carrying multiple epitopes.
Cheong
Wan-Shoo
WS
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Drummer
Heidi Edelgard
HE
Netter
Hans-Jürgen
HJ
D000818:Animals; D001483:Base Sequence; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D022721:Vaccines, Virosome / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus