Vaccine against klebsiella pneumoniae
The present invention relates to a synthetic saccharide of general formula (I) that is related to Klebsiella pneumoniae serotype O1, O2, O2ac, and O8 O-polysaccharide and carbapenem-resistant Klebsiella pneumoniae ST258 O-polysaccharide and conjugate thereof. Said synthetic saccharide, said conjugate and pharmaceutical composition containing said synthetic saccharide or said conjugate are useful for prevention and/or treatment of diseases associated with Klebsiella pneumoniae . Furthermore, the synthetic saccharide of general formula (I) is useful as marker in immunological assays for detection of antibodies against Klebsiella pneumoniae bacteria.
1. A conjugate of general formula (III-8), (III-11), (III-7), (III-2) or (III-3):
wherein
R 1 represents —H, or
n is an integer from 1 to 20;
m is an integer from 0 to 20;
-L- represents —L a -, -L a -L e -, -L a -L b -L e -, or -L a -L d -L e -;
-L a - represents -(CH 2 ) o -, -(CH 2 -CH 2 -O) o -C 2 H 4 -, or -(CH 2 -CH 2 -O) o —CH 2 ;
-L b - represents —O—, —NH—CO—NH—, -NH—CO-CH 2 -NH-, or -NH—CO—;
-L d - represents -(CH 2 ) q -, -(CH(OH) q , —(CF 2 ) q -, -(CH 2 -CH 2 -O) q —C 2 H 4 -, or —(CH 2 -CH 2 -O) q -CH 2 —;
-L e - represents -(CH 2 ) p1 -, -(CF 2 ) p1 -, -C 2 H 4 -(O-CH 2 -CH 2 ) p1 -, —CH 2 -(O-CH 2 -CH 2 ) p1 -, or -(CH 2 ) p1 -O-(CH 2 ) p2 -; and
o, q, p1 and p2 are independently of each other an integer selected from 1, 2, 3, 4, 5, and 6;
-E 1 - represents a covalent bond, —NH—, —O—NH—, —O—, —S—, —CO—, —CH═CH—, —CONH—, —CO—NHNH—,
T- represents
a represents an integer from 1 to 10;
b represents an integer from 1 to 4;
i is an integer selected from 2 to 25; and
CP is non-toxic mutated diphtheria toxin CRM 197 .
2. The conjugate according to claim 1 , wherein
n is an integer from 1 to 10; and
m is an integer from 1 to 10.
3. The conjugate according to claim 1 , wherein
n is an integer from 1 to 10; and
m is 0 or 1.
4. The conjugate according to claim 1 , wherein the conjugate is selected from general formula (III-8), (III-11), (III-7), or (III-2):
wherein R 1 is H, and
n is an integer from 1 to 10.
5. The conjugate according to claim 4 , wherein
-E 1 - represents a covalent bond, —NH—, —CH═CH—, -CONH-,
and
-T- represents
and a is an integer selected from 2, 3, 4, 5 and 6.
6. The conjugate according to claim 5 , wherein -L- represents —(CH 2 ) o — and o is an integer selected from 1, 2, 3, 4, 5 and 6.
7. The conjugate according to claim 6 , wherein i is an integer selected from 2 to 18.
8. The conjugate according to claim 7 , wherein i is an integer selected from 4 to 10.
9. A conjugate, wherein the conjugate comprises
wherein i is an integer selected from 2 to 18.
10. The conjugate according to claim 9 , wherein the conjugate comprises
wherein i is an integer selected from 4 to 10.
11. A conjugate having the formula:
12. A pharmaceutical composition comprising at least one conjugate according to claim 1 as an active ingredient together with at least one pharmaceutically acceptable adjuvant and/or excipient.
13. A pharmaceutical composition comprising at least one conjugate according to claim 4 as an active ingredient together with at least one pharmaceutically acceptable adjuvant and/or excipient.
14. A pharmaceutical composition comprising at least one conjugate according to claim 9 as an active ingredient together with at least one pharmaceutically acceptable adjuvant and/or excipient.
15. A method of inducing immune response against Klebsiella pneumoniae in a human or animal host, said method comprising administering at least one conjugate according to claim 1 to said human or animal host.
16. A method of inducing immune response against Klebsiella pneumoniae in a human or animal host, said method comprising administering at least one conjugate according to claim 4 to said human or animal host.
17. A method of inducing immune response against Klebsiella pneumoniae in a human or animal host, said method comprising administering at least one conjugate according to claim 9 to said human or animal host.
18. The method according to claim 15 , wherein the immune response is induced for the prevention and/or treatment of a disease associated with Klebsiella pneumoniae , wherein the disease is selected from meningitis, urinary tract infection, nosocomial pneumonia, intra-abdominal infections, wound infection, infection of blood, osteomyelitis, bacteremia, septicemia and ankylosing spondylitis.
19. The method according to claim 16 , wherein the immune response is induced for the prevention and/or treatment of a disease associated with Klebsiella pneumoniae , wherein the disease is selected from meningitis, urinary tract infection, nosocomial pneumonia, intra-abdominal infections, wound infection, infection of blood, osteomyelitis, bacteremia, septicemia and ankylosing spondylitis.
20. The method according to claim 17 , wherein the immune response is induced for the prevention and/or treatment of a disease associated with Klebsiella pneumoniae , wherein the disease is selected from meningitis, urinary tract infection, nosocomial pneumonia, intra-abdominal infections, wound infection, infection of blood, osteomyelitis, bacteremia, septicemia and ankylosing spondylitis.
21. The method according to claim 18 , wherein the Klebsiella pneumoniae is selected from O-serotypes comprising or consisting of O1, O2a, O2ac, O2aeh, O2afg, O8, and carbapanem-resistant Klebsiella pneumoniae strain ST 258.
22. The method according to claim 19 , wherein the Klebsiella pneumoniae is selected from O-serotypes comprising or consisting of O1, O2a, O2ac, O2aeh, O2afg, O8, and carbapanem-resistant Klebsiella pneumoniae strain ST 258.
23. The method according to claim 20 , wherein the Klebsiella pneumoniae is selected from O-serotypes comprising or consisting of O1, O2a, O2ac, O2aeh, O2afg, O8, and carbapanem-resistant Klebsiella pneumoniae strain ST 258.