Contructs 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 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 vaccine of claim 1 , wherein the HSV is selected from the group consisting of HSV-1 and HSV-2.
3. The vaccine 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 vaccine 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 vaccine of claim 1 , wherein the at least one antigen is selected from the group consisting of:
a. an influenza virus antigen;
b. a nucleoprotein P influenza virus antigen;
c. a Plasmodium antigen;
d. a Plasmodium antigen selected from the group consisting of thrombospondin-related anonymous protein (TRAP), ring-infected erythrocyte surface antigen (RESA), merozoite surface protein 1 (MSP1), merozoite surface protein 2 (MSP2), merozoite surface protein 3 (MSP3), and glutamate-rich antigen (GLURP);
e. human papilloma virus (HPV) antigen;
f. human papilloma virus HPV16 antigen;
g. HPV E5 protein;
h. HPV E6 protein;
i. HPV E7 protein;
j. a human immunodeficiency virus (HIV) antigen; and
k. an HIV gag antigen.
6. The vaccine of claim 1 , wherein the nucleic acid molecule encodes the amino acid sequence encoded SEQ ID NO:35.
7. The vaccine of claim 1 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:31; SEQ ID NO:32; SEQ ID NO:34; SEQ ID NO:35; SEQ ID NO:36; and SEQ ID NO:37.
8. The vaccine of claim 1 , wherein the fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO:22; SEQ ID NO:23; SEQ ID NO:24; and SEQ ID NO:33.
9. The vaccine of claim 1 , wherein the nucleic acid molecule is in a viral vector.
10. The vaccine of claim 1 , wherein the nucleic acid molecule is naked DNA.
11. The vaccine of claim 1 , wherein the nucleic acid molecule is in a bacterial vector.
12. The vaccine of claim 5 , wherein the second polypeptide segment comprises the HPV E5 protein, the HPV E6 protein, and the HPV E7 protein.
13. The vaccine of claim 1 , wherein the third polypeptide segment comprises the transmembrane domain of the HSV glycoprotein D.
14. A vaccine comprising 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 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.
15. The vaccine of claim 14 , wherein the HSV is selected from the group consisting of HSV-1 and HSV-2.
16. The vaccine of claim 15 , 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.
17. The vaccine of claim 16 , 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.
18. The vaccine of claim 14 , wherein the at least one antigen is selected from the group consisting of:
a. an influenza virus antigen;
b. a nucleoprotein P influenza virus antigen;
c. a Plasmodium antigen;
d. a Plasmodium antigen selected from the group consisting of thrombospondin-related anonymous protein (TRAP), ring-infected erythrocyte surface antigen (RESA), merozoite surface protein 1 (MSP1), merozoite surface protein 2 (MSP2), merozoite surface protein 3 (MSP3), and glutamate-rich antigen (GLURP);
e. human papilloma virus (HPV) antigen;
f. human papilloma virus HPV16 antigen;
g. HPV E5 protein;
h. HPV E6 protein;
i. HPV E7 protein;
j. a human immunodeficiency virus (HIV) antigen; and
k. an HIV gag antigen.
19. The vaccine of claim 14 , wherein the fusion protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO:22; SEQ ID NO:23; SEQ ID NO:24; and SEQ ID NO:33.
20. The vaccine of claim 14 , wherein the fusion protein is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NO:31; SEQ ID NO:32; SEQ ID NO:34; SEQ ID NO:35; SEQ ID NO:36; and SEQ ID NO:37.
21. The vaccine of claim 18 , wherein the second polypeptide segment comprises the HPV E5 protein, the HPV E6 protein, and the HPV E7 protein.
22. The vaccine of claim 14 , wherein the third polypeptide segment comprises the transmembrane domain of the HSV glycoprotein D.