Vaccines against aids comprising cmv/r-nucleic acid constructs

Abstract

The present disclosure provides compositions for eliciting an immune response, including a prophylactic immune response, against human immunodeficiency virus. The composition includes nucleic acid constructs encoding HIV antigenic polypeptides of multiple clades or strains. Methods for eliciting an immune response by administering the composition to a subject are also provided.

1 . A composition capable of eliciting an immune response against HIV in an immunocompetent subject, the composition comprising:
 a plurality of different nucleic acid constructs, each nucleic acid construct comprising a polynucleotide sequence encoding an HIV antigenic polypeptide operably linked to a CMV/R transcription control sequence,   wherein the plurality of nucleic acid constructs encode antigenic polypeptides of a plurality of HIV clades or strains.   
     
     
         2 . A composition capable of eliciting an immune response against HIV in an immunocompetent subject, the composition comprising:
 a plurality of different nucleic acid constructs, each nucleic acid construct comprising a polynucleotide sequence encoding a single HIV antigenic polypeptide, wherein the plurality of nucleic acid constructs encode antigenic polypeptides of a plurality of HIV clades or strains.   
     
     
         3 . The composition of  claim 1  or  2 , wherein the plurality of nucleic acid constructs comprises:
 a first nucleic acid construct comprising a polynucleotide sequence that encodes an HIV Gag polypeptide;   a second nucleic acid construct comprising a polynucleotide sequence that encodes an HIV Pol polypeptide;   a third nucleic acid construct comprising a polynucleotide sequence that encodes an HIV Nef polypeptide; and,   at least one additional nucleic acid construct comprising a polynucleotide sequence that encodes an HIV Env polypeptide.   
     
     
         4 . The composition of claim in  3 , further comprising a plurality of additional nucleic acid constructs, each of which additional nucleic acid constructs comprises a polynucleotide sequence encoding an Env polypeptide of a different HIV clade or strain. 
     
     
         5 . The vaccine composition of  claim 3 , wherein
 the first nucleic acid construct comprises a polynucleotide sequence that encodes a clade B Gag polypeptide;   the second nucleic acid construct comprises a polynucleotide sequence that encodes a clade B Pol polypeptide;   the third nucleic acid construct comprises a polynucleotide sequence that encodes a clade B Nef polypeptide.   
     
     
         6 . The composition of  claim 5 , wherein
 the first nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:20;   the second nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:21; and/or   the third nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:22.   
     
     
         7 . The composition of  claim 5 , the composition further comprising a plurality of additional nucleic acid constructs, wherein
 a first additional nucleic acid construct comprises a polynucleotide sequence that encodes a clade A Env polypeptide;   a second additional nucleic acid construct comprises a polynucleotide sequence that encodes a clade B Env polypeptide; and   a third additional nucleic acid construct comprises a polynucleotide sequence that encodes a clade C Env polypeptide.   
     
     
         8 . The composition of  claim 7 , wherein
 the first additional nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:23;   the second additional nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:24; and/or   the third additional nucleic acid construct encodes a polypeptide with at least 95% sequence identity to SEQ ID NO:25.   
     
     
         9 . The composition of  claim 1 , comprising at least one additional nucleic acid construct, which additional nucleic acid construct comprises a polynucleotide sequence encoding a chimeric Env polypeptide comprising at least a subsequence of a plurality of different HIV clades or strains. 
     
     
         10 . The composition of  claim 1  or  2 , wherein the plurality of different nucleic acid constructs comprise:
 a first nucleic acid construct comprising a polynucleotide sequence encoding a Gag polypeptide;   a second nucleic acid construct comprising a polynucleotide sequence encoding a Pol polypeptide;   a third nucleic acid construct comprising a polynucleotide sequence encoding a Nef polypeptide;   a fourth nucleic acid construct comprising a polynucleotide sequence encoding an Env polypeptide of clade A;   a fifth nucleic acid construct comprising a polynucleotide sequence encoding an Env polypeptide of clade B; and,   a sixth nucleic acid construct comprising a polynucleotide sequence encoding an Env polypeptide of clade C.   
     
     
         11 . The composition of  claim 10 , wherein:
 the first nucleic acid construct comprises a polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:1;   the second nucleic acid construct comprises the polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:2;   the third nucleic acid construct comprises the polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:3;   the fourth nucleic acid construct comprises the polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:4;   the fifth nucleic acid construct comprises the polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:5; and/or,   the sixth nucleic acid construct comprises the polynucleotide sequence with at least 95% sequence identity to SEQ ID NO:6.   
     
     
         12 . The composition of  claim 11 , wherein:
 the first nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:1;   the second nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:2;   the third nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:3;   the fourth nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:4;   the fifth nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:5; and,   the sixth nucleic acid construct comprises the polynucleotide sequence of SEQ ID NO:6.   
     
     
         13 . The composition of  claim 10 , comprising a substantially equal ratio by weight of each of the six nucleic acid constructs. 
     
     
         14 . The composition of  claim 1  or  2 , wherein the composition is capable of eliciting a protective immune response against HIV in an immunocompetent human subject when administered alone or in combination with at least one additional immunogenic composition. 
     
     
         15 . The composition of  claim 1  or  2 , wherein the plurality of different constructs comprises a plurality of plasmids. 
     
     
         16 . The composition of  claim 1  or  2 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         17 . The composition of  claim 1  or  2 , wherein the composition further comprises an adjuvant. 
     
     
         18 . The composition of  claim 1 , wherein the CMV/R transcription control sequence comprises the polynucleotide sequence of SEQ ID NO:26. 
     
     
         19 . A composition capable of eliciting an immune response against HIV in an immunocompetent subject, the composition comprising:
 a plurality of different nucleic acid constructs, each nucleic acid construct comprising a polynucleotide sequence encoding a single HIV antigen operably linked to a transcription control sequence.   
     
     
         20 . A method of eliciting an immune response against HIV comprising administering the composition of  claim 1 ,  2  or  19  to a human subject. 
     
     
         21 . The method of  claim 20 , wherein the immune response is a protective immune response against multiple clades or strains of HIV. 
     
     
         22 . The method of  claim 20 , comprising administering the plurality of nucleic acid constructs intramuscularly. 
     
     
         23 . The method of  claim 20 , comprising administering the plurality of nucleic acid constructs using a needleless delivery device. 
     
     
         24 . The method of  claim 20 , further comprising administering a plurality of viral vectors, wherein the plurality of viral vectors comprises at least one polynucleotide sequence encoding an HIV antigenic polypeptide, wherein the at least one polynucleotide encodes an antigenic polypeptide identical to a polypeptide encoded by a nucleic acid of the composition. 
     
     
         25 . The method of  claim 24 , wherein the viral vectors comprise recombinant adenovirus vectors. 
     
     
         26 . The method of  claim 25 , wherein the recombinant adenovirus vectors are replication deficient adenovirus vectors. 
     
     
         27 . The method of  claim 26 , wherein the plurality of adenovirus vectors comprise:
 a first recombinant adenovirus vector comprising a polynucleotide sequence encoding an HIV Gag polypeptide and an HIV Pol polypeptide;   a second recombinant adenovirus vector comprising a polynucleotide sequence encoding an Env polypeptide of clade A;   a third recombinant adenovirus vector comprising a polynucleotide sequence encoding an Env polypeptide of clade B; and,   a fourth recombinant adenovirus vector comprising a polynucleotide sequence encoding an Env polypeptide of clade C.   
     
     
         28 . The method of  claim 27 , wherein
 the first recombinant adenovirus vector comprises SEQ ID NO:16;   the second recombinant adenovirus vector comprises SEQ ID NO:17;   the third recombinant adenovirus vector comprises SEQ ID NO:18; and   the fourth recombinant adenovirus vector comprises SEQ ID NO:19.   
     
     
         29 . An isolated or recombinant nucleic acid comprising a polynucleotide sequence encoding an HIV antigenic polypeptide operably linked to a CMV/R transcription regulatory sequence. 
     
     
         30 . The nucleic acid of  claim 29 , wherein the nucleic acid comprises a plasmid. 
     
     
         31 . The nucleic acid of  claim 29 , wherein the nucleic acid comprises a viral vector. 
     
     
         32 . The nucleic acid of  claim 29 ,  30  or  31 , wherein the polynucleotide sequence encodes an HIV Gag polypeptide, an HIV Pol polypeptide, an HIV Nef polypeptide, or an HIV Env polypeptide. 
     
     
         33 . The nucleic acid of  claim 32 , wherein the polynucleotide sequence encodes a chimeric HIV polypeptide comprising at least a subsequence of a plurality of HIV clades or strains. 
     
     
         34 . The nucleic acid of  claim 33 , wherein the chimeric HIV polypeptide is an HIV Env polypeptide. 
     
     
         35 . The nucleic acid of  claim 29 ,  30  or  31 , wherein the polynucleotide sequence is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, 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 IID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14 and SEQ ID NO:15. 
     
     
         36 . A polypeptide encoded by a polynucleotide sequence of  claim 35 .