Trimer stabilizing hiv envelope protein mutations

An isolated nucleic acid encoding a recombinant human immunodeficiency virus (HIV) envelope (Env) protein comprising one or more of the following amino acid residues:

• (i) Phe, Leu, Met, or Trp at position 651;
• (ii) Phe, Ile, Met, or Trp at position 655;
• (iii) Asn or Gln at position 535;
• (iv) Val, Ile or Ala at position 589;
• (v) Phe or Trp at position 573;
• (vi) Ile at position 204;
• and/or
• (vii) Phe, Met, or Ile at position 647,
• wherein the HIV Env protein is selected from the group consisting of:
• (1) an HIV Env protein comprising an HIV Env consensus sequence;
• (2) a synthetic HIV Env protein;
• and
• (3) a parent HIV Env protein comprising at least one repair mutation at an amino acid residue that is present at the corresponding position at a frequency of less than 7.5% of HIV Env sequences in a collection of at least 1000 HIV Env sequences, wherein the repair mutation is a substitution by an amino acid residue that is present at the corresponding position at a frequency of at least 10% of HIV Env sequences in said collection;
• and wherein the numbering of the positions is according to the numbering in gp160 of HIV-1 isolate HXB2 having the amino acid sequence of SEQ ID NO:
• 1.

An isolated nucleic acid molecule encoding a recombinant human immunodeficiency virus (HIV) envelope (Env) protein comprising one or more of the following amino acid residues:

• (i) Phe, Leu, Met, or Trp at position 651;
• (ii) Phe, Ile, Met, or Trp at position 655;
• (iii) Asn or Gln at position 535;
• (iv) Val, Ile or Ala at position 589;
• (v) Phe or Trp at position 573;
• (vi) Ile at position 204;
• and/or
• (vii) Phe, Met, or Ile at position 647,
• wherein the HIV Env protein is a HIV Env protein further comprising at least one of the following:
• (a) Cys at positions 501 and 605;
• (b) Pro at position 559;
• or
• (c) Cys at positions 501 and 605 and Pro at position 559;
• and
• the numbering of the positions is according to the numbering in gp160 of HIV-1 isolate HXB2 having the amino acid sequence of SEQ ID NO:
• 1.