MODIFIED GP140 ENVELOPE POLYPEPTIDES OF HIV-1 ISOLATES, COMPOSITIONS, STABILIZED TRIMERIC COMPLEXES, AND USES THEREOF

摘要

This invention provides a modified gp140 envelope polypeptide of an HIV-1 isolate comprising a gp120 polypeptide portion comprising consecutive amino acids and a gp41 ectodomain polypeptide portion comprising consecutive amino acids, said gp41 ectodomain polypeptide portion being modified to comprise isoleucine (I) at an amino acid position equivalent to amino acid position 535; glutamine (Q) at an amino acid position equivalent to amino acid position 543; serine (S) at an amino acid position equivalent to amino acid position 553; lysine (K) at an amino acid position equivalent to amino acid position 567; and arginine (R) at an amino acid position equivalent to amino acid position 588, the amino acid positions being numbered by reference to the HIV-1 isolate KNH1144. This invention also provides nucleic acids encoding such a polypeptide, vectors, host cells, trimeric complexes and compositions thereof. Also provided are antibodies generated against the modified polypeptides and trimeric complexes, and methods of using the modified polypeptides, compositions and trimeric complexes.