Patent
This invention provides a polypeptide derived from E. coli or a fragment thereof, including compositions and methods thereof. In one embodiment, the compositions comprise a polypeptide derived from E. coli or a fragment thereof, and modified O-polysaccharide molecules derived from E. coli lipopolysaccharides or conjugates thereof. In a further aspect, the compositions further comprise modified O-polysaccharide molecules derived from Klebsiella pneumoniae or conjugates thereof.
1 . A method of eliciting an immune response against Escherichia coli ( E. coli ) and Klebsiella pneumoniae ( K. pneumoniae ) in a subject, comprising administering to the subject an effective amount of a composition comprising (a) a saccharide derived from E. coli comprising a structure selected from the group consisting of Formula O1A, Formula O2, Formula O6: K2, Formula O6: K13, Formula O6: K15, Formula O6: K54, Formula O25b, and Formula O75, wherein n is an integer consisting of 31 to 100 in the Formula for each saccharide molecule; and (b) a saccharide derived from a K. pneumoniae type selected from the group consisting of O3, O4, O5, O7, O8, and O12.
2 . The method according to claim 1 , wherein the K. pneumoniae saccharide is derived from K. pneumoniae type O4.
3 . The method according to claim 1 , wherein the K. pneumoniae saccharide is derived from K. pneumoniae type O7.
4 . The method according to claim 1 , wherein the K. pneumoniae saccharide is derived from K. pneumoniae type O3.
5 . The method according to claim 1 , wherein the K. pneumoniae saccharide is derived from K. pneumoniae type O5.
6 . The method according to claim 1 , wherein the composition comprises a saccharide derived from K. pneumoniae type O3 and a saccharide derived from K. pneumoniae type O5.
7 . The method according to claim 1 , wherein the saccharide derived from K. pneumoniae is conjugated to a carrier protein; and the saccharide derived from E. coli is conjugated to a carrier protein.
8 . The method according to claim 1 , wherein the E. coli saccharide further comprises a 3-deoxy-d-manno-oct-2-ulosonic acid (KDO) moiety.
9 . The method according to claim 7 , wherein the carrier protein conjugated to the saccharide derived from E. coli is selected from the group consisting of CRM 197 , diphtheria toxin fragment B(DTFB), DTFB C8, Diphtheria toxoid (DT), tetanus toxoid (TT), fragment C of TT, pertussis toxoid, cholera toxoid, exotoxin A from Pseudomonas aeruginosa ( P. aeruginosa ), detoxified Exotoxin A of P. aeruginosa (EPA), maltose binding protein (MBP), detoxified hemolysin A of Staphylococcus aureus , clumping factor A, clumping factor B, Cholera toxin B subunit (CTB), Streptococcus pneumoniae Pneumolysin, detoxified variants of Streptococcus pneumoniae Pneumolysin, Campylobacter jejuni ( C. jejuni ) AcrA, and C. jejuni natural glycoproteins.
10 . The method according to claim 7 , wherein the carrier protein conjugated to the saccharide derived from K. pneumoniae is selected from the group consisting of CRM 197 , diphtheria toxin fragment B (DTFB), DTFB C8, Diphtheria toxoid (DT), tetanus toxoid (TT), fragment C of TT, pertussis toxoid, cholera toxoid, exotoxin A from Pseudomonas aeruginosa ( P. aeruginosa ), detoxified Exotoxin A of P. aeruginosa (EPA), maltose binding protein (MBP), detoxified hemolysin A of Staphylococcus aureus , clumping factor A, clumping factor B, Cholera toxin B subunit (CTB), Streptococcus pneumoniae Pneumolysin, detoxified variants of Streptococcus pneumoniae Pneumolysin, Campylobacter jejuni AcrA, and C. jejuni natural glycoproteins.
11 . The method according to claim 1 , wherein the immune response comprises opsonophagocytic antibodies against E. coli.
12 . The method according to claim 1 , wherein the immune response protects the subject from an E. coli infection.
13 . The method according to claim 1 , wherein the immune response comprises opsonophagocytic antibodies against K. pneumoniae.
14 . The method according to claim 1 , wherein the immune response protects the subject from a K. pneumoniae infection.