Signature-based human immunodeficiency virus (HIV) envelope (Env) trimer vaccines and methods of using the same

An isolated polypeptide comprising:

• A)
• (a) a human immunodeficiency virus (HIV) envelope (Env) glycoprotein comprising an asparagine residue at position 33, a lysine residue at position 49, a glutamic acid residue at position 130, and a threonine residue at position 132 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (b) a HIV Env glycoprotein comprising an asparagine residue at position 156, a serine residue at position 158, an asparagine residue at position 160, a methionine residue at position 161, a threonine residue at position 162, a threonine residue at position 163, a glutamic acid residue at position 164, a lysine residue at position 165, an arginine residue at position 166, an aspartic acid residue at position 167, a lysine residue at position 168, a lysine residue at position 169, a lysine residue at position 170, a lysine residue at position 171, a valine residue at position 172, and a serine residue at position 173 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (c) a HIV Env glycoprotein comprising a tyrosine residue at position 177, a tyrosine residue at position 223, an isoleucine residue at position 297, a serine residue at position 306, an aspartic acid residue at position 322, a lysine residue at position 335, a serine residue at position 636, an arginine residue at position 644, and an asparagine residue at position 677 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• or
• B)
• (a) a HIV Env glycoprotein comprising an asparagine residue at position 33, a glutamic acid residue at position 49, an aspartic acid residue at position 130, and a lysine residue at position 132 relative residue to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (b) a HIV Env glycoprotein comprising an asparagine residue at position 156, a threonine residue at position 158, an asparagine residue at position 160, an isoleucine residue at position 161, a threonine residue at position 162, a threonine residue at position 163, a serine residue at position 164, a valine residue at position 165, a lysine residue at position 166, a glycine residue at position 167, a lysine residue at position 168, an arginine residue at position 169, a glutamine residue at position 170, a glutamine residue at position 171, a glutamic acid residue at position 172, and a histidine residue at position 173 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (c) a HIV Env glycoprotein comprising a tyrosine residue at position 177, a tyrosine residue at position 223, a valine residue at position 297, a serine residue at position 306, a glutamic acid residue at position 322, a lysine residue at position 335, a serine residue at position 636, an arginine residue at position 644, and an asparagine residue at position 677 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• or
• C)
• (a) a HIV Env glycoprotein comprising an aspartic acid residue at position 62, a valine residue at position 85, a lysine residue at position 160, a threonine residue at position 162, an isoleucine residue at position 184, a threonine residue at position 240, an asparagine residue at position 276, and a threonine residue at position 278 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (b) a HIV Env glycoprotein comprising an asparagine residue at position 295, a threonine residue at position 297, a glycine residue at position 300, an asparagine residue at position 301, a threonine residue at position 303, an arginine residue at position 304, an isoleucine residue at position 307, an isoleucine residue at position 323, a glycine residue at position 324, an aspartic acid residue at position 325, an isoleucine residue at position 326, an arginine residue at position 327, a glutamine residue at position 328, a histidine residue at position 330, an asparagine residue at position 332, and a serine residue at position 334 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (c) a HIV Env glycoprotein comprising an alanine residue at position 336, an asparagine residue at position 339, a threonine residue at position 341, a glutamine residue at position 344, an alanine residue at position 346, an asparagine residue at position 392, a threonine residue at position 394, and a serine residue at position 668 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• or
• D)
• (a) a HIV Env glycoprotein comprising an aspartic acid residue at position 62, a valine residue at position 85, an asparagine residue at position 160, a threonine residue at position 162, an isoleucine residue at position 184, a threonine residue at position 240, an asparagine residue at position 276, and a serine residue at position 278 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (b) a HIV Env glycoprotein comprising a threonine residue at position 295, an isoleucine residue at position 297, a serine residue at position 300, an asparagine residue at position 301, a threonine residue at position 303, an arginine residue at position 304, a valine residue at position 307, an isoleucine residue at position 323, a glycine residue at position 324, an asparagine residue at position 325, an isoleucine residue at position 326, an arginine residue at position 327, a lysine residue at position 328, a tyrosine residue at position 330, a glutamic acid residue at position 332, and an asparagine residue at position 334 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• and/or
• (c) a HIV Env glycoprotein comprising a threonine residue at position 336, an asparagine residue at position 339, a threonine residue at position 341, an asparagine residue at position 344, a serine residue at position 346, an asparagine residue at position 392, a serine residue at position 394, and a serine residue at position 668 relative to the sequence of HXB2 (GenBank Accession No. AF033819.3);
• or
• E) an amino acid sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO:
• 33;
• or
• F) an amino acid sequence having at least 85% sequence identity to the amino acid sequence of SEQ ID NO:
• 34;
• or
• G) an amino acid sequence having at least 97% sequence identity to the amino acid sequence of SEQ ID NO:
• 35;
• or
• H) an amino acid sequence having at least 94% sequence identity to the amino acid sequence of SEQ ID NO:
• 36.