Compositions and methods for generating an immune response
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12Q-001/70
C12N-015/63
C12N-015/33
C12N-015/48
C12N-015/49
A61K-039/21
출원번호
US-0336566
(2003-01-03)
등록번호
US-8623379
(2014-01-07)
발명자
/ 주소
Robinson, Harriet L.
Smith, James
Hua, Jian
출원인 / 주소
Emory University
대리인 / 주소
King & Spalding
인용정보
피인용 횟수 :
1인용 특허 :
47
초록▼
We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV clade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained fro
We have developed DNA and viral vectors that can be used, alone or in combination, as a vaccine against one HIV clade, subtype, or recombinant form of HIV or against multiple HIV clades, subtypes, or recombinant forms. Moreover, the vectors can encode a variety of antigens, which may be obtained from one clade or from two or more different clades, and the antigens selected and/or the manner in which the vectors are formulated (e.g., mixed) can be manipulated to generate a protective immune response against a variety of clades (e.g., the clades to which a patient is most likely to be exposed; with the proportions of the components of the vaccine tailored to the extent of the patient's risk to a particular clade or clades).
대표청구항▼
1. A method of eliciting a cellular and humoral immune response to an HIV antigen in a human subject comprising: (a) administering to the human subject a composition comprising a DNA vector encoding at least: HIV Gag, HIV Pol lacking the integrase domain, HIV Tat, HIV Rev, HIV Vpu, and HIV Env, all
1. A method of eliciting a cellular and humoral immune response to an HIV antigen in a human subject comprising: (a) administering to the human subject a composition comprising a DNA vector encoding at least: HIV Gag, HIV Pol lacking the integrase domain, HIV Tat, HIV Rev, HIV Vpu, and HIV Env, all of which are of a selected HIV chosen from the group consisting of HIV clades A, B, C, D, E, F, G, H, I, J, K, L, and HIV AG, wherein the DNA vector comprises: nucleotides 6,627-9,506 of SEQ ID NO:8 or nucleotides 6,643-10,466 of SEQ ID NO:14; and(b) administering to the subject a composition comprising a modified vaccinia Ankara virus expressing at least one HIV antigen,wherein a cellular and humoral immune response to an HIV antigen is elicited in the human subject. 2. The method of claim 1 wherein the selected HIV is chosen from the group consisting of HIV clade B, HIV clade C, and HIV AG. 3. The method of claim 1 wherein the selected HIV clade is HIV clade B. 4. The method of claim 1 wherein the DNA vector comprises: an antibiotic resistance gene, a lambda T0 terminator and the CMV immediate early promoter. 5. The method of claim 1 wherein the modified vaccinia Ankara virus expresses HIV Gag. 6. The method of claim 1 wherein the modified Ankara virus expresses at least HIV Gag and HIV Pol, wherein the integrase domain of the HIV Pol is deleted. 7. The method of claim 6 wherein the modified Ankara virus expresses at least: HIV Gag; HIV Pol, wherein the integrase domain of the HIV Pol is deleted; and a truncated HIV Env. 8. The method of claim 1 wherein the HIV Gag has a mutation in a zinc finger domain that reduces RNA packaging activity. 9. The method of claim 1 wherein the HIV Pol has a mutation that reduces protease activity. 10. The method of claim 1 wherein the HIV Pol has a mutation that reduces polymerase activity. 11. The method of claim 1 wherein the HIV Pol has a mutation that reduces strand transfer activity. 12. The method of claim 1 wherein the HIV Pol has a mutation that reduces RNase H activity. 13. A method of eliciting a cellular and humoral immune response to an HIV antigen in a human subject comprising: (a) administering to the human subject a composition comprising a DNA vector selected from the group consisting of pGA2/JS7 (SEQ ID NO: 8), pGA1/IN3 (SEQ ID NO:14), pGA1/IN2 (SEQ ID NO: 15), pGA1/IC2 (SEQ ID NO: 11) and pGA1/IC25 (SEQ ID NO: 10); and(b) administering to the human subject a composition comprising a modified vaccinia Ankara virus expressing at least one HIV antigen, wherein a cellular and humoral immune response to an HIV antigen is elicited in the human subject. 14. The method of claim 13 wherein the modified Ankara virus expresses at least HIV Gag and HIV Pol, wherein the integrase domain of the HIV Pol is deleted. 15. The method of claim 14 wherein the modified Ankara virus expresses at least: HIV Gag; HIV Pol, wherein the integrase domain of the HIV Pol is deleted; and a truncated HIV Env. 16. The method of claim 13 wherein the DNA vector is pGA2/JS7 (SEQ ID NO: 8). 17. The method of claim 14 wherein the DNA vector is pGA2/JS7 (SEQ ID NO: 8). 18. The method of claim 15 wherein the DNA vector is pGA2/JS7 (SEQ ID NO: 8).
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