CHEMICALLY MODIFIED BACTERIAL PEPTIDOGLYCAN COMPOSITIONS AND USES THEREOF
Provided are compositions and formulations comprising an isolated Staphylococcus aureus peptidoglycan sacculus comprising an azide-modified D-amino acid and an immunogenic polypeptide attached thereto. The composition can optionally also comprise an adjuvant. Also provided are methods for inducing an immune response in a subject using such compositions and formulations. Kits are also provided.
1 . A composition comprising an isolated Staphylococcus aureus ( S. aureus ) peptidoglycan (PGN) sacculus bonded to an immunogenic polypeptide via a triazole moiety.
2 . The composition of claim 1 , wherein the triazole moiety is a reaction product between an azide-modified D-amino acid on the S. aureus PGN sacculus and a cycloalkyne moiety bonded to the immunogenic polypeptide via a linker moiety.
3 . The composition of claim 2 , wherein the azide-modified D-amino acid is azido-D-alanine (azaDala).
4 . The composition of claim 2 , wherein the linker moiety is a reaction product between an amino acid residue in the immunogenic polypeptide and a crosslinker reagent comprising the cycloalkyne moiety and a peptide-reactive handle.
5 . The composition of claim 4 , wherein the cycloalkyne moiety is a cyclooctyne moiety.
6 . The composition of claim 5 , wherein the cyclooctyne moiety is dibenzocyclooctyne (DBCO).
7 . The composition of claim 4 , wherein the peptide-reactive handle is a maleimide and the amino acid residue in the immunogenic polypeptide is a cysteine residue.
8 . The composition of claim 4 , wherein the peptide-reactive handle is a N-hydroxysuccinimide moiety.
9 . The composition of claim 4 , wherein the crosslinker reagent further comprising one or more ethylene glycol moieties.
10 - 11 . (canceled)
12 . The composition of claim 1 , wherein the S. aureus PGN sacculus is a peptidoglycan sacculus selected from S. aureus strain ATCC 25923, ATCC 29213, SH1000, RN4220, or RN4220 (ΔTarO).
13 . The composition of claim 12 , wherein the S. aureus PGN sacculus is a peptidoglycan sacculus from S. aureus strain SH1000.
14 . The composition of claim 1 , wherein the S. aureus PGN sacculus is bonded to a plurality of different immunogenic polypeptides via triazole moieties.
15 . (canceled)
16 . The composition of claim 1 , wherein the immunogenic polypeptide is a SARS-CoV-2 Spike protein or a fragment thereof or a cancer neoantigen.
17 - 22 . (canceled)
23 . A formulation comprising the composition of claim 1 and a pharmaceutically acceptable excipient.
24 . (canceled)
25 . A method of inducing an immune response in a subject, the method comprising administering to the subject a therapeutically effective amount of the formulation of claim 23 .
26 . The method of claim 25 , wherein the method elicits an antibody response and/or a T-cell response in the subject.
27 . (canceled)
28 . The method of claim 25 , wherein the immunogenic polypeptide is a SARS-CoV-2 Spike protein or a fragment thereof, and wherein the formulation is administered in an amount capable of eliciting a protective immune response against the SARS-CoV-2 Spike protein in the subject.
29 . (canceled)
30 . The method of claim 25 , wherein the immunogenic polypeptide is a protein expressed in a cancer cell, and wherein the formulation is administered in an amount capable of eliciting a protective immune response against a cancer.
31 . (canceled)
32 . The method of claim 30 , wherein the subject has, has had, or is at risk of developing the cancer.
33 . (canceled)
34 . A kit comprising the formulation of claim 23 packaged in a container and instructions for the administration thereof.
35 - 38 . (canceled)