Modified cytomegalovirus proteins and stabilized complexes
AssigneeGlaxosmithkline Biologicals SA
InventorsEnrico Malito, Matthew James Bottomley, Andrea Carfi, Sumana Chandramouli, Kate Luisi
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Abstract
Described are mutant human cytomegalovirus (HCMV) pentamer complex polypeptides, methods of making them, and their use in HCMV protein complexes and compositions. In particular, the use of the modified HCMV polypeptides to stabilize HCMV complexes or unmask a pentamer epitope is described.
Claims12
A Human Cytomegalovirus (HCMV) polypeptide comprising a mutant glycoprotein L (gL), wherein the mutant gL comprises a substitution mutation at one or more of the amino acid residues H177, G224, G140, G145, D146, G218, L119, C233 and P272, relative to the sequence set forth in SEQ ID NO:
- 7, or at a corresponding position in other HCMV gL polypeptides, wherein the residues are substituted with an amino acid selected from the group consisting of tryptophan (W), phenylalanine (F), tyrosine (Y), and leucine (L).
A Human Cytomegalovirus (HCMV) polypeptide comprising a mutant glycoprotein L (gL), wherein the mutant gL comprises:
- (i) a substitution mutation at one or more of the amino acid residues H267, H236, H245, and G161 relative to the sequence set forth in SEQ ID NO:
- 7, or at a corresponding position in other HCMV gL polypeptides, wherein the residues are substituted with an amino acid selected from the group consisting of tryptophan (W), phenylalanine (F), methionine (M), cysteine (C), alanine (A), leucine (L), isoleucine (I), valine (V) and proline (P),
- and (ii) a substitution mutation at amino acid residue C233 relative to the sequence set forth in SEQ ID NO:
- 7, or at a corresponding position in other HCMV gL polypeptides, wherein the amino acid residue is substituted with an amino acid selected from the group consisting of tryptophan (W), phenylalanine (F), methionine (M), alanine (A), leucine (L), isoleucine (I), valine (V) and proline (P).
A Human Cytomegalovirus (HCMV) polypeptide comprising a mutant glycoprotein L (gL), wherein the mutant gL comprises a substitution mutation at one or more of the amino acid residues G161, D163, G224, G218, R166, G140, R160, and A150, relative to the sequence set forth in SEQ ID NO:
- 7, or at a corresponding position in other HCMV gL polypeptides, wherein the residues are substituted with a cysteine (C).
Dependencies are inferred from the claim text.