Anti-HIV vaccine constructed based on amino acid mutations in attenuated live EIAV vaccine

1. An isolated polynucleotide comprising a nucleotide sequence that encodes an antigenic HIV-1 envelope protein or antigenic fragment thereof, wherein the antigenic HIV-1 envelope protein or antigenic fragment thereof comprises a modification, and wherein the modification is a substitution of a leucine residue at a position corresponding to position 52 in SEQ ID NO: 1 by a glutamic acid or an aspartic acid residue.

2. A DNA construct comprising the polynucleotide of claim 1 operably linked to a promoter.

3. The DNA construct of claim 2 , which is selected from: pDRVISV145M1R (CGMCC No. 2508), pDRVISV145M2R (CGMCC No. 2509), pDRVISV145M3R (CGMCC No. 2510), pDRVISV145M4R (CGMCC No. 2511), pDRVISV145M5R (CGMCC No. 2512), pDRVISV1452M (CGMCC No. 2513), and pDRVISV1455M (CGMCC No. 2514).

4. A DNA vaccine comprising the DNA construct of claim 2 or 3 together with a pharmaceutical acceptable adjuvant.

5. A recombinant viral vector vaccine which comprises a recombinant viral vector carrying a polynucleotide of claim 1 and a pharmaceutical acceptable adjuvant.

6. The recombinant viral vector vaccine according to claim 5 , wherein the recombinant viral vector is selected from a vaccinia vector, an adenovirus vector, an adeno-associated virus vector, a sendai virus vector, a herpes simplex virus vector, a human papillomavirus vector, and a retroviral vector.

7. The recombinant viral vector vaccine according to claim 5 , wherein the recombinant viral vector is a replication-competent viral vector.

8. The recombinant viral vector vaccine according to claim 7 , wherein the replication-competent viral vector is a recombinant replication-competent vaccinia vector.

9. The recombinant viral vector vaccine according to claim 8 , wherein the recombinant replication-competent vaccinia vector is a recombinant replication-competent vaccinia Tian Tan strain.

10. The isolated polynucleotide of claim 1 , wherein the amino acid sequence of the polypeptide or fragment contains at least the following mutations:

the deletion of the threonine residue at the position corresponding to position 138 in SEQ ID NO:1; and

the substitution of the asparagine residue at the position corresponding to position 139 in SEQ ID NO:1 by a glutamine residue.

11. The isolated polynucleotide of claim 1 , wherein the amino acid sequence of the polypeptide or fragment contains at least the following mutations:

Deletion of the threonine residue at a position corresponding to position 138 in SEQ ID NO: 1;

substitution of the asparagine residue at a position corresponding to position 139 in SEQ ID NO:1 by, a glutamine residue;

substitution of the arginine residue at a position corresponding to position 166 in SEQ ID NO:1 by a glutamic acid or an aspartic acid residue;

substitution of the isoleucine residue at a position corresponding to position 184 in SEQ ID NO:1 by a glutamic acid or an aspartic add residue;

substitution of the aspartic add residue at a position corresponding to position 185 in SEQ ID NO:1 by a lysine, an arginine or a histidine residue;

substitution of the threonine residue at a position corresponding to position 188 in SEQ ID NO:1 by a glutamine or an asparagine residue;

substitution of the glycine residue at a position corresponding to position 235 in SEQ ID NO:1 by an arginine, a lysine or a histidine residue;

substitution of the glycine residue at a position corresponding to position 237 in SEQ ID NO:1 by a glutamine or an asparagine residue; and

substitution of the threonine residue at a position corresponding to position 240 in SEQ ID NO:1 by a tyrosine residue.

12. The isolated polynucleotide of claim 1 , wherein the HIV-1 envelope protein is selected from the group consisting of gp120, gp128, gp140, gp140TM, gp145, gp150, gp160, and an equivalent thereof.

13. The isolated polynucleotide of claim 1 , wherein the HIV-1 envelope protein is gp145 of HIV-1 CN54 having the amino acid sequence of SEQ ID NO:2.

14. The isolated polynucleotide of according to claim 1 , wherein the polypeptide or fragment further contains a modification selected from the group consisting of deletion or addition of glycosylation site, deletion or rearrangement of loop region, deletion of CFI region, and combination thereof.

15. A method for treating a HIV-1 virus infection comprising a step of administering the DNA vaccine of claim 5 and/or the recombinant viral vector vaccine of claim 6 to a subject in need thereof.

16. The polynucleotide of claim 1 , further comprising a modification selected from: substitution of the arginine residue at a position corresponding to position 166 in SEQ ID NO:1 by a glutamic acid or an aspartic acid residue; substitution of the isoleucine residue at a position corresponding to position 184 in SEQ ID NO:1 by a glutamic acid or an aspartic acid residue; substitution of the aspartic acid residue at a position corresponding to position 185 in SEQ ID NO:1 by a lysine, an arginine or a histidine residue; substitution of the threonine residue at a position corresponding to position 188 in SEQ ID NO:1 by a glutamine or an asparagine residue; substitution of the glycine residue at a position corresponding to position 235 in SEQ ID NO:1 by an arginine, a lysine or a histidine residue; substitution of the glycine residue at a position corresponding to position 237 in SEQ ID NO:1 by a glutamine or an asparagine residue; and substitution of the threonine residue at a position corresponding to position 240 in SEQ ID NO:1 by a tyrosine residue, and combinations thereof.