Expression and Characterization of HIV-1 Envelope Protein Associated with Broadly Cross Reactive Neutralizing Antibody Response

Abstract

The present invention relates to HIV-1 envelope proteins from a donor with non-progressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus neutralizing antibody. The invention also relates to isolated or purified proteins and protein fragments that share certain amino acids at particular positions with the foregoing HIV-1 proteins.

1 . An isolated HIV envelope protein or fragment thereof which, when administered to a mammal, induces the production of broadly cross-reactive neutralizing anti-serum against multiple strains of HIV-1. 
     
     
         2 . An isolated HIV envelope protein comprising the amino acid sequence of SEQ ID NO: 1. 
     
     
         3 . An isolated HIV envelope protein or fragment thereof comprising a proline at a position corresponding to amino acid residue 313, a methionine at a position corresponding to amino acid residue 314 and a glutamine at a position corresponding to amino acid residue 325 of SEQ ID NO:1. 
     
     
         4 . An isolated HIV envelope protein or fragment thereof comprising a V3 region having the amino acid sequence P M X 1  X 2  X 3  X 4  X 5  X 6  X 7  X 8  X 9  X 10  Q, wherein X 1 -X 10  are a natural or non-natural amino acid. 
     
     
         5 . (canceled) 
     
     
         6 . An immunogenic composition comprising an isolated HIV-1 envelope protein or fragment thereof of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . An isolated nucleic acid molecule encoding the HIV-1 envelope protein or fragment thereof of  claim 1 . 
     
     
         8 . A fusion protein comprising all or a portion of a microbiological antigen into which the protein of  claim 1  has been inserted. 
     
     
         9 . A recombinant delivery vector encoding a fusion protein comprising all or a portion of a microbiological antigen into which the protein of  claim 1  has been inserted. 
     
     
         10 . (canceled) 
     
     
         11 . An immunogenic composition comprising the recombinant delivery vector of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
         12 . A recombinant delivery vector encoding an attenuated virus further comprising a nucleotide sequence encoding the protein  claim 1 . 
     
     
         13 . The recombinant delivery vector of  claim 12  wherein the attenuated virus is selected from the group comprising HIV, encephalitis virus, poliovirus, poxvirus and vaccinia virus. 
     
     
         14 . (canceled) 
     
     
         15 . An immunogenic composition comprising the recombinant delivery vector  claim 12  and a pharmaceutically acceptable carrier. 
     
     
         16 . A method of generating antibodies in a mammal comprising administering the protein of  claim 1  or fragments thereof in an amount sufficient to induce the production of the antibodies. 
     
     
         17 . A method of generating antibodies in a mammal comprising administering a DNA or mRNA sequence encoding the protein of  claim 1  or fragments thereof, in an amount sufficient to induce the production of the antibodies. 
     
     
         18 . The method of  claim 17 , wherein said DNA is naked DNA. 
     
     
         19 . A diagnostic reagent comprising the isolated HIV-1 envelope protein of  claim 1  or fragments thereof. 
     
     
         20 . A method of detecting HIV-1 antibodies in a sample comprising the step of determining whether antibodies in the sample bind to one or more of the HIV-1 envelope proteins or fragments thereof  claim 1 . 
     
     
         21 . A cyclic peptide comprising the amino acid sequence of  claim 3 . 
     
     
         22 . An isolated antibody which specifically recognizes the protein of  claim 3 .