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 method of inducing an immune response comprising providing to a subject in need thereof a vaccine comprising a nucleic acid molecule which encodes a fusion protein, wherein the fusion protein comprises:
a. 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 mature glycoprotein D;
b. 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
c. 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 method of claim 1 , wherein the HSV is selected from the group consisting of HSV-1 and HSV-2.
3. The method of claim 2 , wherein the first polypeptide segment comprises an amino acid sequence selected from the group consisting of:
a. amino acids 26-265 of SEQ ID NO:27;
b. amino acids 26-265 of SEQ ID NO:29;
c. amino acids 1-244 of the glycoprotein D;
d. amino acids 1-288 of the glycoprotein D; and
e. amino acids 1-294 of a mature HSV glycoprotein D with the exception that amino acid 294 is alanine instead of tryptophan.
4. The method of claim 3 , wherein the first polypeptide segment is encoded by a nucleic acid sequence comprising nucleotides 76-795 of SEQ ID NO:26; or nucleotides 350-1069 of SEQ ID NO:28.
5. The method of claim 1 , wherein the nucleic acid molecule is in a viral vector.
6. The method of claim 1 , wherein the nucleic acid molecule is naked DNA.
7. The method of claim 1 , wherein the nucleic acid molecule is in a bacterial vector.
8. The method of claim 1 , wherein the second polypeptide segment comprises the HPV E5 protein, the HPV E6 protein, and the HPV E7 protein.
9. The method of claim 1 , wherein the third polypeptide segment comprises the transmembrane domain of the HSV glycoprotein D.