Stabilization of human immunodeficiency virus (hiv) envelopes
OwnerDaniel Wrapp, Kevin Saunders +1inventors
InventorsDaniel Wrapp, Kevin Saunders, Barton F. Haynes
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Abstract
Disclosed are stabilized type I fusion proteins (e.g., HIV envelope proteins). For HIV-1, the stabilization of Env due to the disclosed modifications are compatible and, in some embodiments, synergistic with stabilization mutations known as SOS, IP and SOSIP. The disclosed stabilized Env proteins retain the antigenicity of the unmodified protein.
Claims61
A modified type I fusion protein from a retrovirus, comprising substituted amino acids at one or more of positions 536, 545, 568 and 569 (HXB2 numbering).
A modified HIV envelope protein (Env) comprising prolines at positions 559, 568 and 569.
A method for modifying an envelope protein (Env) from a retrovirus, comprising:
- substituting one amino acid in an unmodified Env protein with a substituting amino acid to obtain a modified Env protein;
- and
- determining a stability of the modified Env protein as compared to a stability of the unmodified Env protein.
A method for modifying an envelope protein (Env) from a retrovirus, comprising:
- identifying amino acid positions within flexible loops of an unmodified Env protein;
- substituting one or more of the identified amino acid positions in the unmodified Env protein with a proline to produce a modified Env;
- and
- determining yield of the modified Env in an expression system.
A method for modifying an envelope protein (Env) of HIV-1, HIV-2 or SIV, comprising:
- selecting an Env protein that has a threonine at position 568, a leucine at position 569, or a threonine at position 568 and a leucine at position 569;
- and
- substituting the threonine at position 568, the leucine at position 569, or the threonine at position 568 and the leucine at position 569 with proline.
A method for modifying an envelope protein (Env) of HIV, comprising:
- identifying amino acids at position 568, 569, or 568 and 569 in the Env;
- and
- substituting one or more of the amino acid(s) with proline or glycine.
Dependencies are inferred from the claim text.