IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0706576
(2007-02-13)
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등록번호 |
US-8277816
(2012-10-02)
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발명자
/ 주소 |
- Yusibov, Vidadi
- Mett, Vadim
- Musiychuck, Konstantin
- Skarjinskaia, Marina
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 |
피인용 횟수 :
4 인용 특허 :
88 |
초록
▼
The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to antigens and vaccines useful in prevention of infection by Bacillus anthracis. Provided are recombinant protein antigens, compositions, and methods for the production and use of
The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to antigens and vaccines useful in prevention of infection by Bacillus anthracis. Provided are recombinant protein antigens, compositions, and methods for the production and use of such antigens and vaccine compositions.
대표청구항
▼
1. An isolated antigen comprising a component of Bacillus anthracis virulence factor fused to a LicKM protein; wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:
1. An isolated antigen comprising a component of Bacillus anthracis virulence factor fused to a LicKM protein; wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1; andwherein the LicKM protein comprises an amino acid sequence with at least 95% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10. 2. An immunogenic composition comprising an antigen comprising a component of Bacillus anthracis virulence factor fused to a LicKM protein and a pharmaceutically acceptable carrier; wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1;wherein the LicKM protein comprises an amino acid sequence with at least 95% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10;and wherein the composition is capable of eliciting an immune response upon administration to a subject. 3. An immunogenic composition comprising: at least two antigens, each of which comprises a component of Bacillus anthracis virulence factor having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1, wherein at least one of the antigens further comprises a LicKM protein, and wherein the LicKM protein comprises an amino acid sequence with at least 95% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10. 4. The immunogenic composition of claim 3, wherein at least one of the antigens comprises a virulence factor component consisting of an amino acid sequence selected from the group consisting of about amino acid residues 1-137 of SEQ ID NO.:2, amino acid residues 251-263 of SEQ ID NO.:2, amino acid residues 138-250 of SEQ ID NO.:2, amino acid residues 264-283 of SEQ ID NO.:2, amino acid residues 429-551 of SEQ ID NO.:2, amino acid residues 306-385 of SEQ ID NO:2, and amino acid residues 552-776 of SEQ ID NO.:2. 5. The immunogenic composition of claim 3, wherein at least one of the antigens comprises the amino acid sequence of SEQ ID NO.: 14. 6. The immunogenic composition of claim 3, wherein at least one of the antigens comprises a virulence factor component consisting of an amino acid sequence selected from the group consisting of about amino acid residues 1-250 of SEQ ID NO.:1, amino acid residues 241-456 of SEQ ID NO.:1, amino acid residues 477-595 of SEQ ID NO.:1, and amino acid residues 608-735 of SEQ ID NO.:1. 7. The immunogenic composition of claim 3, wherein at least one of the antigens comprises the amino acid sequence of SEQ ID NO.: 12. 8. The immunogenic composition of claim 3, wherein the virulence factor component consists of SEQ ID NO.:15. 9. The immunogenic composition of claim 3, wherein the virulence factor component is fused to the LicKM protein at the LicKM N-terminus or at the LicKM C-terminus, or is fused to a loop structure that is exposed on the surface of LicKM and is located far from the LicKM active domain. 10. The immunogenic composition of claim 3, wherein the virulence factor component of at least one antigen comprises at least two amino acid sequences with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 11. The immunogenic composition of claim 10, wherein at least one antigen comprises SEQ ID NO.:4 and at least one antigen comprises amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, or amino acid residues 552-776 of SEQ ID NO.: 2. 12. The immunogenic composition of claim 3, wherein the antigen is produced by a plant selected from a transgenic plant and a plant which transiently expresses the antigen. 13. The immunogenic composition of claim 3, wherein the composition comprises antigen which is purified, partially purified, or unpurified from plant cells, a plant, seeds, fruit, or an extract thereof. 14. The immunogenic composition of claim 3, further comprising at least one vaccine adjuvant. 15. The immunogenic composition of claim 14 wherein the adjuvant is selected from the group consisting of alum, MF59, MALP2, and saponin. 16. A method for inducing an immune response in a subject, comprising administering to a subject an effective amount of an anti-anthrax immunogenic 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 immunogenic composition comprises an antigen comprising a component of Bacillus anthracis virulence factor fused to a LicKM protein, wherein the LicKM protein comprises an amino acid sequence with at least 95% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10; andwherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 17. A method for inducing an immune response in a subject, comprising administering to a subject an effective amount of an anti-anthrax immunogenic composition, wherein the immunogenic composition comprise at least two antigens, each of which comprises a component of Bacillus anthracis virulence factor having an amino acid sequence with at least 95% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1, wherein at least one of the antigens further comprises a LicKM protein, wherein the LicKM protein comprises an amino acid sequence with at least 95% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10, and 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. 18. The isolated antigen of claim 1, wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 97% identity to a sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residue residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 19. The isolated antigen of claim 1, wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 98% identity to a sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 20. The isolated antigen of claim 1, wherein the virulence factor component consists of an amino acid sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 21. The isolated antigen of claim 1, wherein the LicKM protein has an amino acid sequence with at least 97% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10. 22. The isolated antigen of claim 1, wherein the virulence factor component is fused to the LicKM protein at the LicKM N-terminus or at the LicKM C-terminus, or is fused to a loop structure that is exposed on the surface of LicKM and is located far from the LicKM active domain. 23. The isolated antigen of claim 1, wherein the antigen has the amino acid sequence of SEQ ID NO.: 12. 24. The isolated antigen of claim 1, wherein the antigen has the amino acid sequence of SEQ ID NO.: 14. 25. The isolated antigen of claim 1, wherein the antigen is produced by a plant selected from a transgenic plant and a plant which transiently expresses the antigen. 26. The isolated antigen of claim 1, wherein the antigen is purified, partially purified, or unpurified from plant cells, a plant, seeds, fruit, or an extract thereof. 27. The immunogenic composition of claim 2, wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 97% identity to a sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 28. The immunogenic composition of claim 2, wherein the virulence factor component comprises at least one domain having an amino acid sequence with at least 98% identity to a sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 29. The immunogenic composition of claim 2, wherein the virulence factor component consists of an amino acid sequence selected from the group consisting of SEQ ID NO.: 4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 30. The immunogenic composition of claim 2, wherein the LicKM protein has an amino acid sequence with at least 97% identity to SEQ ID NO.: 8 or SEQ ID NO.: 10. 31. The immunogenic composition of claim 2, wherein the virulence factor component is fused to the LicKM protein at the LicKM N-terminus or at the LicKM C-terminus, or is fused to a loop structure that is exposed on the surface of LicKM and is located far from the LicKM active domain. 32. The immunogenic composition of claim 2, wherein the antigen has the amino acid sequence of SEQ ID NO.: 12. 33. The immunogenic composition of claim 2, wherein the antigen has the amino acid sequence of SEQ ID NO.: 14. 34. The immunogenic composition of claim 2, wherein the antigen is produced by a plant selected from a transgenic plant and a plant that transiently expresses the antigen. 35. The immunogenic composition of claim 2, wherein the composition comprises antigen that is purified, partially purified, or unpurified from plant cells, a plant, seeds, fruit, or an extract thereof. 36. The immunogenic composition of claim 2, further comprising at least one vaccine adjuvant. 37. The immunogenic composition of claim 34, wherein the adjuvant is selected from the group consisting of alum, MF59, MALP2, and saponin. 38. The immunogenic composition of claim 3, wherein each antigen comprises a component of Bacillus anthracis virulence factor having an amino acid sequence with at least 97% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID NO.: 2, amino acid residues 264-283 of SEQ ID NO.: 2, amino acid residues 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and amino acid residues 608-735 of SEQ ID NO.: 1. 39. The immunogenic composition of claim 3, wherein each antigen comprises a component of Bacillus anthracis virulence factor having an amino acid sequence with at least 98% identity to a sequence selected from the group consisting of SEQ ID NO.:4, SEQ ID NO: 6, SEQ ID NO: 15, amino acid residues 1-137 of SEQ ID NO.: 2, amino acid residues 251-263 of SEQ ID NO.: 2, amino acid residues 138-250 of SEQ ID residues residue 429-551 of SEQ ID NO.: 2, amino acid residues 306-385 of SEQ ID NO.: 2, amino acid residues 552-776 of SEQ ID NO.: 2, amino acid residues 1-250 of SEQ ID NO.: 1, amino acid residues 251-456 of SEQ ID NO.: 1, amino acid residues 477-595 of SEQ ID NO.: 1, and about amino acid residues 608-735 of SEQ ID NO.: 1.
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