Modified hiv env polypeptides

Abstract

Polynucleotide encoding modified HIV Env polypeptides are disclosed. The Env polypeptides are modified so as to expose at least part of the CD4 binding region. Methods of diagnosis, treatment and prevention using the polynucleotides and polypeptides are also provided.

1 . A construct comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26. 
     
     
         2 . A vaccine composition comprising an immunogenic modified HIV Env polypeptide of a selected variant of HIV, the modified HIV Env polypeptide having at least one amino acid deleted relative to the wild-type Env polypeptide of the selected variant in the region corresponding to residues 420 to 436 numbered relative to HXB-2 (SEQ ID NO:1), such that epitopes that are not exposed in the wild-type Env polypeptide of the selected variant are exposed in the modified Env polypeptide. 
     
     
         3 . The vaccine composition of  claim 2  wherein one amino acid is deleted. 
     
     
         4 . The vaccine composition of  claim 2  wherein more than one amino acid is deleted. 
     
     
         5 . The vaccine composition of  claim 2  wherein at least one of amino acid residues 427, 428, and 429 is deleted. 
     
     
         6 . The vaccine composition of  claim 2  wherein the V1 and V2 regions of the polypeptide are truncated. 
     
     
         7 . The vaccine composition of  claim 5  wherein the V1 and V2 regions of the polypeptide are truncated. 
     
     
         8 . The vaccine composition of  claim 2  wherein the selected variant is HIV strain SF162 (SEQ ID NO:2). 
     
     
         9 . The vaccine composition of  claim 2  further comprising an adjuvant. 
     
     
         10 . The vaccine composition of  claim 5  further comprising an adjuvant. 
     
     
         11 . A method of inducing an immune response in subject comprising administering a polynucleotide in an amount sufficient to induce an immune response in the subject, wherein the polynucleotide encodes an immunogenic modified HIV Env polypeptide of a selected variant of HIV, the modified HIV Env polypeptide having at least one amino acid deleted relative to the wild-type Env polypeptide of the selected variant in the region corresponding to residues 420 to 436 numbered relative to HXB-2 (SEQ ID NO:1), such that epitopes that are not exposed in the wild-type Env polypeptide of the selected variant are exposed in the modified Env polypeptide. 
     
     
         12 . The method of  claim 11  further comprising administering an adjuvant to the subject. 
     
     
         13 . A method of inducing an immune response in a subject comprising steps of:
 (a) administering a first composition comprising a polynucleotide encodes an immunogenic modified HIV Env polypeptide of a selected variant of HIV, the modified HIV Env polypeptide having at least one amino acid deleted relative to the wild-type Env polypeptide of the selected variant in the region corresponding to residues 420 to 436 numbered relative to HXB-2 (SEQ ID NO:1), such that epitopes that are not exposed in the wild-type Env polypeptide of the selected variant are exposed in the modified Env polypeptide in a priming step; and   (b) administering a second composition comprising the modified HIV Env polypeptide as a booster in an amount sufficient to induce an immune response in the subject.   
     
     
         14 . The method of  claim 13  wherein the first composition or second composition further comprise an adjuvant. 
     
     
         15 . The method of  claim 13  wherein the first and second compositions further comprise an adjuvant.