Contructs for enhancing immune responses

Patent metadata

Field	Value
Publication number	US-10328146-B2
Application number	US-201715639296-A
Country	US
Kind code	B2
Filing date	Jun 30, 2017
Priority date	Aug 28, 2006
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

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.

First claim

What is claimed:

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.

Assignees

• Wistar Inst

Inventors

• Ertl Hildegund C J
• Lasaro Marcio O
• Ferreira Luis C S

Classifications

• A61P31/22

  for herpes viruses · CPC title

• A61K2039/57

  characterised by the type of response, e.g. Th1, Th2 · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• C12N2710/16622

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• A61K39/245 Primary

  Herpetoviridae, e.g. herpes simplex virus · CPC title