Polypeptide-antigen conjugates with non-natural amino acids
AssigneeVaxcyte, Inc.
InventorsJeffery Fairman, Jon H. Heinrichs, Wei Chan
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Abstract
Methods for the production of immunogenic compositions containing a non-natural amino acid are disclosed. The non-natural amino acid can be a site for attachment of antigens, such as bacterial capsular polysaccharides, to make immunogenic conjugates. Bio-orthogonal attachment chemistry incorporated into the non-natural amino acids allows for more efficient and potent antigen presentation to the immune system, simplified purification, and more well-defined structure of these semi-synthetic immunogens.
Claims17
A composition comprising at least 21 distinct crosslinked carrier protein-antigen conjugates, wherein each of the distinct crosslinked carrier protein-antigen conjugates comprises:
- (i) an antigen, wherein the antigen is a distinct serotype of a capsular polysaccharide antigen from Streptococcus pneumoniae,
- wherein there is a distinct crosslinked carrier protein-antigen conjugate for each of the capsular polysaccharide antigens of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F and a distinct crosslinked carrier protein-antigen conjugate for each of at least eight additional capsular polysaccharide antigens of serotypes selected from the group consisting of 2, 6C, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 20, 20A, 20B, 22F, 23A, 23B, 24F, 24B, 31, 33F, 34, 35B, 35F and 38;
- and
- (ii) a carrier protein, wherein the carrier protein comprises a polypeptide comprising at least one T-cell activating epitope and at least 95% sequence identity to SEQ ID NO:
- 1, wherein a 2-amino-3-(4-(azidomethyl)phenyl)propanoic acid (pAMF) non-natural amino acid (nnAA) is substituted for a naturally occurring amino acid at residues 34, 213, 245, 265, 386, and 527 numbered according to SEQ ID NO:1,
- wherein the capsular polysaccharide antigen is conjugated to the nnAAs in the carrier protein.
Dependencies are inferred from the claim text.