Nucleic acid vectors for immunization
A dimeric protein comprising a first fusion protein and a second fusion protein, wherein the first fusion protein comprises a targeting domain, a leucine zipper domain, and an antigen; and wherein the second fusion protein comprises a targeting domain, a leucine zipper domain, and optionally an antigen. Nucleic acid vectors encoding proteins of the invention are provided, particularly for use in nucleic acid vaccination.
1. A nucleic acid vector encoding a dimeric protein comprising a first fusion protein and a second fusion protein,
wherein the first fusion protein comprises:
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) a viral antigen;
and wherein the second fusion protein comprises:
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) optionally an antigen.
2. A nucleic acid vector encoding a fusion protein comprising:
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) a viral antigen.
3. The nucleic acid vector according to claim 1 wherein an additional sequence selected from the group consisting of a nucleotide sequence encoding a secretory sequence, a nucleotide sequence encoding a leader sequence, and a nucleotide sequence encoding a retention sequence is fused to the nucleotide sequences encoding the first fusion protein or the second fusion protein.
4. A composition comprising two nucleic acid vectors according to claim 2 , said vectors encoding a dimeric protein comprising a first fusion protein and a second fusion protein, wherein the first fusion protein comprises:
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) a viral antigen;
and wherein the second fusion protein comprises
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) optionally an antigen.
5. An isolated host cell comprising a nucleic acid vector according to claim 1 .
6. A composition comprising the nucleic acid vector according to claim 1 or claim 2 and a suitable pharmaceutical carrier.
7. An isolated host cell comprising two nucleic acid vectors according to claim 1 , each of said vectors encoding a dimeric protein comprising a first fusion protein and a second fusion protein, wherein the first fusion protein comprises:
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) a viral antigen;
and wherein the second fusion protein comprises
(i) CTLA-4 or the V-like domain thereof,
(ii) a leucine zipper domain, and
(iii) optionally an antigen.
8. The composition according to claim 4 , further comprising a suitable pharmaceutical carrier.
9. The nucleic acid vector according to claim 2 , wherein an additional sequence selected from the group consisting of a nucleotide sequence encoding a secretory sequence, a nucleotide sequence encoding a leader sequence, and a nucleotide sequence encoding a retention sequence is fused to the nucleotide sequence encoding the fusion protein.
10. The nucleic acid vector according to claim 3 or 9 , wherein said additional sequence is selected from the group consisting of a nucleotide sequence encoding the human tissue-type plasminogen activator signal/pro sequence, a nucleotide sequence encoding the ER retention sequence KDEL (SEQ ID NO:22) and a nucleotide sequence encoding the GPI anchor signal.
11. The nucleic acid vector according to claim 1 , wherein the first fusion protein or the second fusion protein comprises a GCN4 leucine zipper domain.
12. The nucleic acid vector according to claim 1 , wherein the second fusion protein comprises a viral antigen.
13. The nucleic acid vector according to claim 2 , wherein the fusion protein comprises a GCN4 leucine zipper domain.
14. The nucleic acid vector according to claim 4 , wherein the first fusion protein or the second fusion protein comprises a GCN4 leucine zipper domain.
15. The nucleic acid vector according to claim 4 , wherein the second fusion protein comprises a viral antigen.
16. The nucleic acid vector according to claim 7 , wherein the first fusion protein or the second fusion protein comprises a GCN4 leucine zipper domain.
17. The nucleic acid vector according to claim 7 , wherein the second fusion protein comprises a viral antigen.