antigens, vaccine compositions, and related methods

• US 8,945,580 B2
• Filed: 02/25/2013
• Issued: 02/03/2015
• Est. Priority Date: 07/11/2007
• Status: Active Grant

• Current Assignee: iBio, Inc.
• Original Assignee: iBio, Inc.
• Inventors: Yusibov, Vidadi, Mett, Vadim, Musiychuk, Konstantin
• Primary Examiner(s): Baskar, Padma V
• Application Number:
  US13/775,677
• Publication Number:
  US 20130149327A1
• Time in Patent Office: 708 Days
• US Class Current: 424/192.1
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/6068 Other bacterial proteins, e.g. OMP
• CPC Class Codes: A61K 39/025 Enterobacteriales, e.g. Enterobacter
• CPC Class Codes: A61K 39/0291 Yersinia
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/24 from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides antigens and vaccines useful in prevention of infection by Yersinia pestis. The present invention provides pharmaceutical compositions of such antigens and/or vaccines. The present invention provides methods for the production of Y. pestis protein antigens in plants, as well as methods for their use in the treatment and/or prevention of Y. pestis infection.

Claims

1. An isolated antigen comprising two Yersinia proteins fused to a LicKM protein, wherein a first of the two Yersinia proteins comprises a full-length F1 protein that is at least 95% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 95% identical to the sequence set forth as SEQ ID NO;

9.

2. The isolated antigen of claim 1, wherein a first of the two Yersinia proteins comprises a full-length F1 protein that is at least 98% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 98% identical to the sequence set forth as SEQ ID NO;

9.

3. The isolated antigen of claim 1, wherein a first of the two Yersinia proteins comprise the amino acid sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises the amino acid sequence set forth as SEQ ID NO;

9.

4. The isolated antigen of claim 1, wherein the two Yersinia proteins are fused to the LicKM protein as an N-terminal fusion, a C-terminal fusion, a surface loop insertion fusion, or a combination thereof.

5. The isolated antigen of claim 1, wherein the antigen comprises an amino acid sequence that is at least 95% identical to the sequence set forth as SEQ ID NO:

27.

6. The isolated antigen of claim 1, wherein the antigen comprises an amino acid sequence that is at least 98% identical to the sequence set forth as SEQ ID NO:

27.

7. The isolated antigen of claim 1, wherein the antigen comprises the amino acid sequence set forth as SEQ ID NO:

27.

8. A vaccine composition comprising a pharmaceutically acceptable carrier and an antigen comprising two Yersinia proteins fused to a LicKM protein, wherein a first of the two Yersinia proteins comprises a full-length F1 protein that is at least 95% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 95% identical to the sequence set forth as SEQ ID NO;

9, and wherein the composition is capable of eliciting an immune response upon administration to a subject.

9. The vaccine composition of claim 8, wherein a first of the two Yersinia proteins comprises a full-length F1 protein that is at least 98% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 98% identical to the sequence set forth as SEQ ID NO;

9.

10. The vaccine composition of claim 8, wherein a first of the two Yersinia proteins comprises the amino acid sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises the amino acid sequence set forth as SEQ ID NO;

9.

11. The vaccine composition of claim 8, wherein the two Yersinia proteins are fused to the LicKM protein as an N-terminal fusion, a C-terminal fusion, a surface loop insertion fusion, or a combination thereof.

12. The vaccine composition of claim 8, wherein the antigen comprises an amino acid sequence that is at least 95% identical to the sequence set forth as SEQ ID NO:

27.

13. The vaccine composition of claim 8, wherein the antigen comprises an amino acid sequence that is at least 98% identical to the sequence set forth as SEQ ID NO:

27.

14. The vaccine composition of claim 8, wherein the antigen comprises the amino acid sequence set forth as SEQ ID NO:

27.

15. The vaccine composition of claim 8, wherein the antigen is produced in a transgenic plant or in a plant transiently expressing the antigen.

16. The vaccine composition of claim 8, wherein the composition comprises an antigen that is purified or partially purified from plant cells, a plant, seeds, fruit, or an extract thereof.

17. The vaccine composition of claim 8, further comprising at least one vaccine adjuvant.

18. The vaccine composition of claim 17, wherein the adjuvant is selected from the group consisting of complete Freund'"'"'s adjuvant, incomplete Freund'"'"'s adjuvant, alum, MF59, saponin, aluminum hydroxide, QuilA, and macrophage-activating lipopeptide (Malp-2).

19. A method for inducing an immune response against Yersinia infection in a subject, comprising administering to the subject an effective amount of an anti-Yersinia vaccine composition, wherein the administration is sufficient to stimulate production of antigen specific antibodies or stimulate a cellular immune response by the subject, thereby inducing an immune response, wherein the vaccine composition comprises an antigen comprising two Yersinia proteins fused to a LicKM protein, wherein a first of the two Yersinia proteins comprises a full-length F 1 protein that is at least 95% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 95% identical to the sequence set forth as SEQ ID NO;

9.

20. The method of claim 19, wherein a first of the two Yersinia proteins comprises a full-length F1 protein that is at least 98% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises a full-length LcrV protein that is at least 98% identical to the sequence set forth as SEQ ID NO;

9.

21. The method of claim 19, wherein a first of the two Yersinia proteins comprises the amino acid sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein a second of the two Yersinia proteins comprises the amino acid sequence set forth as SEQ ID NO;

9.

22. The method of claim 19, wherein the two Yersinia proteins are fused to the LicKM protein as an N-terminal fusion, a C-terminal fusion, a surface loop insertion fusion, or a combination thereof.

23. The method of claim 19, wherein the antigen comprises an amino acid sequence that is at least 95% identical to the sequence set forth as SEQ ID NO:

27.

24. The method of claim 19, wherein the antigen comprises an amino acid sequence that is at least 98% identical to the sequence set forth as SEQ ID NO:

27.

25. The method of claim 19, wherein the antigen comprises the amino acid sequence set forth as SEQ ID NO:

27.

26. The method of claim 19, wherein the composition is administered orally, intranasally, subcutaneously, intravenously, intraperitoneally, or intramuscularly.

27. The method of claim 19, wherein the composition comprises plant produced antigen, and wherein the administration is an oral administration to the subject.

28. A composition comprising a first isolated antigen and a second antigen, wherein the first antigen comprises a first Yersinia protein fused to a LicKM protein, wherein the first Yersinia protein comprises a full-length F1 protein that is at least 95% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7, wherein the second antigen comprises a second Yersinia protein fused to a LicKM protein, and wherein the second Yersinia protein comprises a full-length LcrV protein that is at least 95% identical to the sequence set forth as SEQ ID NO;

9.

29. The composition of claim 28, wherein the first Yersinia protein comprises the amino acid sequence set forth as SEQ ID NO:

1, 3, 5, or 7, and wherein the second Yersinia protein comprises the amino acid sequence set forth as SEQ ID NO;

9.