Enhanced activity of HIV vaccine using a second generation immunomodulatory oligonucleotide
The invention relates to the therapeutic use of a second generation immunomodulatory oligonucleotide in combination with HIV-1 antigen or immunogen to enhance the ability to reduce the risk HIV infection and to control the progression of HIV infection to prevent AIDS Related Complex (ARC) and AIDS.
1 . An HIV-1 specific immunogenic composition comprising:
a) HIV-1 antigen, either alone or admixed with IFA to yield HIV immunogen; and
b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1); wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
2 . An HIV-1 specific immunogenic composition comprising
a) gp120 depleted HV-1 antigen, either alone or admixed with IFA to yield HIV immunogen, and
b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1) wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
3 . A method for enhancing HIV specific immunity comprising administering to a mammal an immunogenic composition according to claim 1 or 2 .
4 . The method according to claim 3 , wherein the HIV-1 antigen or HIV immunogen and the immunomodulatory oligonucleotide are administered simultaneously.
5 . The method according to claim 3 , wherein the HIV-1 antigen or HIV immunogen and the immunomodulatory oligonucleotide are administered sequentially.
6 . The method according to claim 3 , wherein the HIV-1 antigen or HIV immunogen is formulated or mixed with the immunomodulatory oligonucleotide.
7 . A method for preventing HIV infection in a mammal comprising administering to the mammal an immunogenic composition comprising
a) HIV-1 antigen, either alone or admixed with IFA, and
b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′(SEQ ID NO: 1), wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
8 . The method according to claim 7 , wherein the HIV-1 antigen or HIV immunogen and the immunomodulatory oligonucleotide are administered simultaneously.
9 . The method according to claim 7 , wherein the HIV-1 antigen or HIV immunogen and the immunomodulatory oligonucleotide are administered sequentially.
10 . The method according to claim 8 , wherein the HIV-1 antigen or HIV immunogen is formulated or mixed with the immunomodulatory oligonucleotide.
11 . A method for inhibiting the progression of HIV infection to AIDS comprising administering to a mammal an immunogenic composition comprising a) HIV-1 antigen or HIV immunogen, either alone or admixed with an adjuvant, and b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1), wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
12 . The method according to claim 11 , wherein the HIV-1 antigen or immunogen and the immunomodulatory oligonucleotide are administered simultaneously.
13 . The method according to claim 11 , wherein the HIV-1 antigen or immunogen and the immunomodulatory oligonucleotide are administered sequentially.
14 . The method according to claim 12 , wherein the HIV-1 antigen or immunogen is formulated or mixed with the immunomodulatory oligonucleotide.
15 . A method for treating AIDS in a mammal comprising administering to the mammal an immunogenic composition comprising a) HIV-1 antigen, either alone or admixed with an adjuvant, and b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1) wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
16 . The method according to claim 15 , wherein the HIV-1 antigen or immunogen and the immunomodulatory oligonucleotide are administered simultaneously.
17 . The method according to claim 15 , wherein the HIV-1 antigen and the immunomodulatory oligonucleotide are administered sequentially.
18 . The method according to claim 16 , wherein the HIV-1 antigen is formulated or mixed with the immunomodulatory oligonucleotide.
19 . A pharmaceutical composition comprising:
a) HIV-1 antigen, either alone or admixed with IFA;
b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1); and
c) a physiologically acceptable carrier
wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine.
20 . A kit comprising the components:
a) HIV-1 antigen, either alone or admixed with IFA; and
b) an immunomodulatory oligonucleotide having the structure 5′-TCTGTCRTTCT-X-TCTTRCTGTCT-5′ (SEQ ID NO: 1);
wherein X is a glycerol linker and R is 2′-deoxy-7-deazaguanosine, and wherein said kit components, when combined, produce an immunogenic composition.