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US 12,544,435 B2Granted
Neisserial surface protein a (NSPA) variants and methods of use thereof
AssigneeThe Regents of the University of California
InventorsPeter T. Beernink, Dhaarini Raghunathan
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Abstract
Variant Neisserial surface protein A (NspA) with reduced binding to human factor H (FH) are provided. These variants are useful for eliciting antibodies that are bactericidal for at least one strain of N. meningitidis. Compositions comprising such proteins, and methods of use of such proteins are disclosed.
Claims21
A variant Neisserial surface protein (NspA), wherein the variant NspA comprises an amino acid sequence at least 90% identical to the amino acid sequence of SEQ ID NO:
- 1 and comprises at least one of:
- (a) an amino acid substitution of the lysine (K) at position 72 with an uncharged amino acid or a negatively charged amino acid;
- (b) an amino acid substitution of the aspartic acid (D) at position 77 with an uncharged amino acid or a positively charged amino acid;
- (c) an amino acid substitution of the aspartic acid (D) at position 113 with an uncharged amino acid or a positively charged amino acid, wherein when the amino acid substitution at position 113 is with histidine, the variant NspA does not comprise a substitution of valine at position 112 with alanine;
- and
- (d) an amino acid substitution of the aspartic acid (D) at position 118 with an uncharged amino acid or a positively charged amino acid, wherein the uncharged amino acid comprises:
- a non-polar side chain and is selected from the group consisting of glycine, alanine, valine, leucine, methionine and isoleucine;
- a polar side chain and is selected from the group consisting of serine, threonine, cysteine, proline, and glutamine;
- or a non-polar, aromatic side chain and is selected from the group consisting of phenylalanine, tyrosine, and tryptophan,
- wherein the amino acid substitutions are relative to the amino acid sequence of SEQ ID NO:1.
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Dependencies are inferred from the claim text.