Rational vaccine design for hepatitis C virus
Compositions and methods are provided relating to HCV E2 protein and modifications thereto which enhance the immunogenicity of the protein for vaccine development with respect to the generation of a neutralizing immune response.
1. A modified Hepatitis C Virus (HCV) E2 polypeptide comprising an amino acid sequence aligning with SEQ ID NO:1, but numbered according to an E1-E2 polypeptide where residue 1 of SEQ ID NO:1 is numbered as residue 383; b) deletion of 384-409 or 384-404; and c) amino substitutions N417Q, N423Q, N448Q and N532Q.
2. The polypeptide of claim 1 , further comprising substitution of the amino acid present at one more or residues 437, 627 and 631 with asparagine; and introduction of a serine or threonine at one or more of residues 439, 629 and 633.
3. The polypeptide of claim 1 , further comprising an amino acid substitution selected from E431A, E431S, and E431G.
4. The polypeptide of claim 1 , further comprising the amino acid modifications Y632A and D535A.
5. An immunogenic composition comprising:
a modified HCV E2 polypeptide as set forth in claim 1 ; and
a pharmaceutically acceptable excipient.
6. An immunogenic composition of claim 5 , further comprising an adjuvant.
7. The immunogenic composition of claim 5 , further comprising a virus-like particle.