Vaccine

Abstract

This invention relates to novel HIV polypeptide and polynucleotide fusions of Gag, Pol and Nef which are useful in immunogenic compositions and vaccines. The invention relates in particular to a polypeptide which comprises Nef or an immunogenic fragment thereof, and p17 Gag and/or p24 Gag or immunogenic fragments thereof, wherein when both p17 and p24 Gag are present there is at least one HIV antigen or immunogenic fragment between them. The polypeptide may also comprise Pol or RT or an immunogenic fragment thereof.

1 . A polynucleotide encoding a fusion polypeptide comprising a Nef polypeptide, an RT polypeptide, a p17 Gag polypeptide, and a p24 Gag polypeptide wherein there is at least one HIV antigen between the p17 Gag polypeptide and the p24 Gag polypeptide. 
     
     
         2 . The polynucleotide of  claim 1 , wherein the RT polypeptide is p66. 
     
     
         3 . The polynucleotide of  claim 1 , wherein the RT polypeptide is truncated at the C terminus such that it lacks the carboxy terminal RNase H domain. 
     
     
         4 . The polynucleotide of  claim 1 , wherein the RT polypeptide is p51. 
     
     
         5 . The polynucleotide of  claim 1 , wherein the fusion protein comprises from N-terminal to C-terminal: p24-RT-Nef-p17. 
     
     
         6 . The polynucleotide of  claim 5 , wherein the fusion protein comprises from N-terminal to C-terminal: p24-p51RT-Nef-p17. 
     
     
         7 . The polynucleotide of  claim 1 , wherein the fusion protein comprises SEQ ID NO:2. 
     
     
         8 . The polynucleotide of  claim 7 , comprising SEQ ID NO:1. 
     
     
         9 . The polynucleotide of  claim 1 , wherein the fusion protein comprises SEQ ID NO:15. 
     
     
         10 . The polynucleotide of  claim 9 , comprising SEQ ID NO:14. 
     
     
         11 . The polynucleotide of  claim 1 , wherein the fusion protein comprises SEQ ID NO:19. 
     
     
         12 . The polynucleotide of  claim 11 , comprising SEQ ID NO:18. 
     
     
         13 . The polynucleotide of  claim 5 , wherein the amino acid at the position corresponding to position 592 in SEQ ID NO:2 is not methionine. 
     
     
         14 . The polynucleotide of  claim 13 , where said amino acid is lysine. 
     
     
         15 . A pharmaceutical composition comprising the polynucleotide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition of  claim 15 , further comprising an adjuvant. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the adjuvant comprises a Th1 inducing adjuvant. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the TH1 inducing adjuvant comprises QS21, 3D-MPL, or a combination of QS21 and 3D-MPL.