Mutant forms of streptolysin O
AssigneeNovartis AG
InventorsGiuliano Bensi, Immaculada Margarit Y Ros, Emiliano Chiarot, Guido Grandi, Maria Scarselli
Life of this patent
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Abstract
Forms of GAS25 (streptolysin O) which are not toxic but which still maintain the ability to induce protection against S. pyogenes are useful in vaccine compositions to induce protection against S. pyogenes.
Claims27
A purified mutant streptolysin O (SLO) protein comprising an amino acid alteration to the amino acid sequence of wild-type SLO selected from the group consisting of:
- (a) a substitution of glutamine for proline at amino acid position 427;
- (b) a substitution of lysine for proline at amino acid position 427;
- (c) a substitution of glycine for proline at amino acid position 427;
- (d) a substitution of leucine for proline at amino acid position 427;
- and
- (e) a substitution of phenylalanine for tryptophan at amino acid position 535, wherein the amino acid positions are numbered according to SEQ ID NO:
- 1.
A vaccine composition comprising (a) a mutant streptolysin O (SLO) protein;
- and (b) a pharmaceutically acceptable carrier, wherein the mutant SLO protein comprises an amino acid alteration to the amino acid sequence of wild-type SLO selected from the group consisting of:
- (i) a substitution of glutamine for proline at amino acid position 427;
- (ii) a substitution of lysine for proline at amino acid position 427;
- (iii) a substitution of glycine for proline at amino acid position 427;
- (iv) a substitution of phenylalanine for tryptophan at amino acid position 535;
- (v) a substitution of glycine for cysteine at amino acid position 530;
- (vi) a deletion of alanine at position 248;
- (vii) a substitution of leucine for proline at amino acid position 427;
- and
- (viii) a substitution of phenylalanine for tryptophan at amino acid position 535, wherein the amino acid positions are numbered according to SEQ ID NO:
- 1.
A method of making a vaccine for the treatment of infection by Streptococcus pyogenes comprising combining (a) a mutant streptolysin O (SLO) protein;
- and (b) a pharmaceutically acceptable carrier, wherein the mutant SLO protein comprises an amino acid alteration to the amino acid sequence of wild-type SLO selected from the group consisting of:
- (i) a substitution of glutamine for proline at amino acid position 427;
- (ii) a substitution of lysine for proline at amino acid position 427;
- (iii) a substitution of glycine for proline at amino acid position 427;
- (iv) a substitution of phenylalanine for tryptophan at amino acid position 535;
- (v) a substitution of glycine for cysteine at amino acid position 530;
- (vi) a deletion of alanine at position 248;
- (vii) a substitution of leucine for proline at amino acid position 427;
- and
- (viii) a substitution of phenylalanine for tryptophan at amino acid position 535.
A method of inducing an immune response against Streptococcus pyogenes comprising administering to an individual in need thereof an effective amount of the vaccine composition comprising (a) a mutant streptolysin O (SLO) protein;
- and (b) a pharmaceutically acceptable carrier, wherein the mutant SLO protein comprises an amino acid alteration to the amino acid sequence of wild-type SLO selected from the group consisting of:
- (i) a substitution of glutamine for proline at amino acid position 427;
- (ii) a substitution of lysine for proline at amino acid position 427;
- (iii) a substitution of glycine for proline at amino acid position 427;
- (iv) a substitution of phenylalanine for tryptophan at amino acid position 535;
- (v) a substitution of glycine for cysteine at amino acid position 530;
- (vi) a deletion of alanine at position 248;
- (vii) a substitution of leucine for proline at amino acid position 427;
- and
- (viii) a substitution of phenylalanine for tryptophan at amino acid position 535, wherein the amino acid positions are numbered according to SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.