Stabilized filovirus glycoprotein trimers
AssigneeJanssen Vaccines & Prevention B.V.
InventorsJohannes LANGEDIJK, Lucy RUTTEN, Sven BLOKLAND
Life of this patent
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Abstract
Filovirus glycoprotein mutations that stabilize the trimeric form of the glycoprotein are provided. The Filovirus glycoproteins have certain amino acid substitutions at specified positions in the glycoprotein sequence. The Filovirus glycoproteins described herein have an improved percentage of trimer formation and/or an improved trimer yield as compared to a Filovirus glycoprotein that does not have one or more of the indicated amino acid substitutions. Also provided are nucleic acid molecules and vectors encoding the Filovirus glycoproteins, as well as compositions containing the Filovirus glycoproteins, nucleic acid, and vectors.
Claims23
A recombinant Filovirus glycoprotein, comprising a non-charged amino acid residue, at position 588, wherein the numbering of the positions is according to the numbering of the GP in SEQ ID NO:
- 1 (Z/Zaire/Yambuku/1976/057935) and wherein the non-charged amino acid residue is not a cysteine.
(canceled)
A method of improving the trimer formation of a Filovirus glycoprotein, the method comprising substituting an amino acid residue at position 588 of the Filovirus glycoprotein for a non-charged amino acid residue, wherein the numbering of the positions is according to the numbering of the GP in SEQ ID NO:
- 1 (Z/Zaire/Yambuku/1976/057935), and wherein the non-charged amino acid residue is not a cysteine.
A composition comprising:
- a) at least one of:
- a recombinant Filovirus glycoprotein, comprising a non-charged amino acid residue, at position 588, wherein the numbering of the positions is according to the numbering of the GP in SEQ ID NO:
- 1 (Z/Zaire/Yambuku/1976/057935) and wherein the non-charged amino acid residue is not a cysteine;
- a trimeric complex comprising a noncovalent oligomer of three recombinant Filovirus glycoproteins, each recombinant Filovirus glycoprotein comprising a non-charged amino acid residue, at position 588, wherein the numbering of the positions is according to the numbering of the GP in SEQ ID NO:
- 1 (Z/Zaire/Yambuku/1976/057935) and wherein the non-charged amino acid residue is not a cysteine;
- a particle displaying on its surface the recombinant Filovirus glycoprotein;
- an isolated nucleic acid molecule encoding the recombinant Filovirus glycoprotein;
- and
- a vector comprising the isolated nucleic acid molecule operably linked to a promoter;
- and
- b) a pharmaceutically acceptable carrier.
A recombinant Filovirus glycoprotein, wherein the Filovirus glycoprotein is selected from the group consisting of:
- 1) a Zaire Ebolavirus Mayinga glycoprotein comprising the amino acid sequence of SEQ ID NO:
- 2
- 2) a Zaire Ebolavirus Mayinga glycoprotein with a deletion between amino acid residues 320 and 476, comprising the amino acid sequence of SEQ ID NO:
- 6;
- 3) a Zaire Ebolavirus Makona GP glycoprotein comprising the amino acid sequence of SEQ ID NO:
- 10
- 4) a Zaire Ebolavirus Makona GP glycoprotein with a deletion between amino acid residues 314 and 472, comprising the amino acid sequence of SEQ ID NO:
- 14;
- 5) a Zaire Ebolavirus Kikwit glycoprotein comprising the amino acid sequence of SEQ ID NO:
- 19;
- 6) a Zaire Ebolavirus Kikwit glycoprotein with a deletion between amino acid residues 314 and 472, comprising the amino acid sequence of SEQ ID NO:
- 23;
- and
- 7) a Marburg glycoprotein with a deletion between amino acid residues 255 and 423, comprising the amino acid sequence of SEQ ID NO:
- 27,
- wherein the numbering of the positions is according to the numbering of the GP in SEQ ID NO:
- 1 (Z/Zaire/Yambuku/1976/057935).
Dependencies are inferred from the claim text.