Constructs for enhancing immune responses
Chimeric protein constructs including a herpesvirus glycoprotein D (gD) and a heterologous polypeptide that interact with herpes virus entry mediator (HVEM) and enhance and enhance an immune response against the heterologous polypeptide and methods for their use are provided.
1. A fusion protein, wherein the fusion protein comprises:
a first polypeptide segment comprising at least amino acids 1-240 of a mature Herpes simplex virus (HSV) glycoprotein D, wherein the first polypeptide segment does not comprise a full length glycoprotein D;
a second polypeptide segment comprising at least one antigen, wherein the at least one antigen is not an HSV glycoprotein D antigen, wherein the N terminus of the second polypeptide segment is linked to the C terminus of the first polypeptide segment; and
a third polypeptide segment comprising a C terminal portion of the HSV glycoprotein D, wherein the N terminus of the third polypeptide segment is linked to the C terminus of the second polypeptide segment.
2. The fusion protein of claim 1 , wherein the HSV is HSV-1.
3. The fusion protein of claim 2 , wherein the first polypeptide segment comprises amino acids 26-265 of SEQ ID NO:27.
4. The fusion protein of claim 1 , which comprises the amino acid sequence SEQ ID NO:24.
5. The fusion protein of claim 1 , wherein the second polypeptide segment comprises an E5 protein, an E6 protein and an E7 protein from HPV.
6. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence SEQ ID NO:23.
7. The fusion protein of claim 1 , wherein the fusion protein comprises the amino acid sequence SEQ ID NO:22.
8. The fusion protein of claim 1 , wherein the fusion protein is encoded by the nucleic acid sequence SEQ ID NO:32.
9. The fusion protein of claim 1 wherein the fusion protein comprises the amino acid sequence SEQ ID NO:33.
10. The fusion protein of claim 1 , wherein third polypeptide segment comprises the transmembrane domain of the HSV glycoprotein D.
11. A method of inducing an immune response, comprising providing to a subject in need thereof a fusion protein of claim 1 .
12. The method of claim 11 , wherein the fusion protein is provided by administering to the subject a nucleic acid molecule which encodes the fusion protein.
13. The method of claim 11 , wherein the fusion protein comprises the amino acid sequence SEQ ID NO:24.