Methods and compositions related to glycoprotein-immunoglobulin fusions
Disclosed herein are compositions and methods for eliciting immune responses against HCV antigens. In particular embodiments, the compounds and methods elicit immune responses against all or a segment of HCV glycoprotein E1 and/or HCV glycoprotein E2.
1. A polypeptide composition comprising:
a first polypeptide consisting essentially of an amino acid sequence that is at least 98% identical to SEQ ID NO:9 or SEQ ID NO:11; and
a second polypeptide comprising a carboxy terminal light chain immunoglobulin polypeptide and an amino terminal glycoprotein polypeptide,
wherein the first and second polypeptides are in a complex forming at least one heterodimeric polypeptide.
2. The composition of claim 1 , wherein the glycoprotein of the second polypeptide is a Hepatitis C virus glycoprotein.
3. The composition of claim 2 wherein the glycoprotein of the second polypeptide is an HCV E2 or E1 glycoprotein, wherein the first polypeptide and the viral glycoprotein of the second polypeptide assemble to form an HCVE1/E2 glycoprotein complex.
4. The composition of claim 3 , wherein the HCV E1 glycoprotein segment of the second polypeptide consists essentially of an amino acid sequence that is at least 90% identical to SEQ ID NO:4.
5. The composition of claim 1 , wherein the second polypeptide consists essentially of an amino acid sequence that is at least 90% identical to SEQ ID NO:10 or SEQ ID NO:12.
6. A polypeptide composition comprising:
a first polypeptide comprising a carboxy terminal immunoglobulin heavy chain polypeptide and an amino terminal glycoprotein polypeptide; and
a second polypeptide consisting essentially of an amino acid sequence that is at least 99% identical to SEQ ID NO:10 or SEQ ID NO:12,
wherein the first and second polypeptides are in a complex forming at least one heterodimeric polypeptide.
7. The composition of claim 1 , further comprising a polypeptide tetramer comprising two first polypeptides and two second polypeptides.
8. The composition of claim 1 , wherein the first polypeptide and/or the second polypeptide further comprise one or more of a histidine tag and/or a protease cleavage site.
9. A pharmaceutical and/or vaccine composition capable of treating and/or preventing a viral infection, the pharmaceutical and/or vaccine composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient, wherein the pharmaceutical and/or vaccine composition is capable of eliciting an immune response to the first and/or second polypeptide.
10. The composition of claim 6 , wherein the glycoprotein of the first polypeptide is a Hepatitis C virus glycoprotein.
11. The composition of claim 10 , wherein the glycoprotein of the first polypeptide is an HCV E2 or E1 glycoprotein, wherein the second polypeptide and the viral glycoprotein of the first polypeptide assemble to form an HCVE1/E2 glycoprotein complex.
12. The composition of claim 11 , wherein the HCV E1 glycoprotein segment of the first polypeptide consists essentially of an amino acid sequence that is at least 90% identical to SEQ ID NO:4.
13. The composition of claim 6 , wherein the first polypeptide consists essentially of an amino acid sequence that is at least 80% identical to SEQ ID NO:9 or SEQ ID NO:11.
14. The composition of claim 6 , further comprising a polypeptide tetramer comprising two first polypeptides and two second polypeptides.
15. The composition of claim 6 , wherein the first polypeptide and/or the second polypeptide further comprise one or more of a histidine tag and/or a protease cleavage site.
16. A pharmaceutical and/or vaccine composition capable of treating and/or preventing a viral infection, the pharmaceutical and/or vaccine composition comprising the composition of claim 6 and a pharmaceutically acceptable excipient, wherein the pharmaceutical and/or vaccine composition is capable of eliciting an immune response to the first and/or second polypeptide.