Yersinia pestis antigens, vaccine compositions, and related methods

• US 8,404,252 B2
• Filed: 07/11/2008
• Issued: 03/26/2013
• Est. Priority Date: 07/11/2007
• Status: Active Grant

• Current Assignee: iBio, Inc.
• Original Assignee: Fraunhofer USA Inc. (Fraunhofer-Institut für Nachrichtentechnik HHI)
• Inventors: Yusibov, Vidadi, Mett, Vadim, Musiychuk, Konstantin
• Primary Examiner(s): BASKAR, PADMAVATHI
• Application Number:
  US12/668,258
• Publication Number:
  US 20110027304A1
• Time in Patent Office: 1,719 Days
• Field of Search: None
• US Class Current: 424/255.1
• 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 a Yersinia pestis protein fused to a modified thermostable protein;

wherein the Yersinia pestis 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, and wherein the modified thermostable protein is a LicKM protein.

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

1, 3, 5, or 7.

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

1, 3, 5, or 7.

4. The isolated antigen of claim 1, wherein the Yersinia pestis protein fused to the modified thermostable protein is one or more of an N-terminal fusion, a C-terminal fusion, or a surface loop insertion fusion protein.

5. A vaccine composition comprising a pharmaceutically acceptable carrier and an antigen comprising a Yersinia pestis protein fused to a modified thermostable protein, wherein the Yersinia pestis 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 modified thermostable protein is a LicKM protein; and

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

6. The vaccine composition of claim 5, wherein the Yersinia pestis protein comprises an amino acid sequence that is at least 98% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7.

7. The vaccine composition of claim 5, wherein the Yersinia pestis protein comprises the amino acid sequence set forth as SEQ ID NO.:

1, 3, 5, or 7.

8. The vaccine composition of claim 5, wherein the Yersinia pestis protein fused to the modified thermostable protein is one or more of an N-terminal fusion, a C-terminal fusion, or a surface loop insertion fusion protein.

9. The vaccine composition of claim 5, wherein the antigen is produced in a plant selected from a transgenic plant and a plant transiently expressing the antigen.

10. The vaccine composition of claim 5, wherein the composition comprises antigen which is purified, partially purified, or unpurified from plant cells, a plant, seeds, fruit, or an extract thereof.

11. The vaccine composition of claim 5, further comprising at least one vaccine adjuvant.

12. The vaccine composition of claim 11, 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).

13. A method for inducing a protective immune response against Yersinia pestis infection in a subject comprising administering to a subject an effective amount of an anti-Yersinia pestis 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 a protective immune response;

wherein the vaccine composition comprises an antigen comprising a Yersinia pestis protein fused to a modified thermostable protein; and

wherein the Yersinia pestis 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; and

wherein the modified thermostable protein is a LicKM protein.

14. The method of claim 13, wherein the composition is administered orally, intranasally, subcutaneously, intravenously, intraperitoneally, or intramuscularly.

15. The method of claim 14, wherein the composition is administered orally via feeding plant cells to the subject.

16. The method of claim 13, wherein the subject is human.

17. The method of claim 13, wherein the Yersinia pestis protein comprises an amino acid sequence that is at least 98% identical to the sequence set forth as SEQ ID NO:

1, 3, 5, or 7.

18. The method of claim 13, wherein the Yersinia pestis protein comprises the amino acid sequence set forth as SEQ ID NO:

1, 3, 5, or 7.