US2011200638A1PendingUtilityA1
Bacterial vaccine
Est. expirySep 11, 2021(expired)· nominal 20-yr term from priority
Inventors:Arthur Keith TurnerJudith GreenwoodJonathan Clive StephensJuliet Claire BeavisMichael J. Darsley
A61K 39/0258A61K 2039/522A61K 2039/53A61P 31/04C12N 15/70A61K 2039/521A61P 37/04C07K 14/245Y02A50/30A61K 39/00
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Claims
Abstract
A bacterial cell which expresses three or more coli surface (CS) antigens and methods of making such a cell. The cell is useful in making vaccines against diarrhea.
Claims
exact text as granted — not AI-modified1 . A composition that induces an immune response against three or more coli surface (CS) antigens comprising a bacterial cell which expresses said three or more CS antigens.
2 . A composition according to claim 1 , wherein the cell is an E. coli cell.
3 . A composition according to claim 2 , wherein the cell is an enterotoxigenic E. coli (ETEC) cell.
4 . A composition according to claim 1 , wherein the CS antigens are ETEC CS antigens selected from CS1, CS2, CS3, CS4, CS5 and CS6.
5 . A composition according to claim 1 , wherein the cell expresses CS1, CS2 and CS3.
6 . A composition according to claim 1 , wherein the cell expresses CS4, CS5 and CS6.
7 . A composition according to claim 1 , wherein the cell expresses CS1, CS3 and CS4.
8 . A composition according to claim 1 , wherein the cell is attenuated by deletion or inactivation of a gene.
9 . A composition according to claim 8 , wherein the cell is attenuated by deletion or inactivation of one or more of aroA, aroC, aroD, aroE, pur, htrA, ompC, ompF, ompR, cya, crp, phoP, phoQ, surA, rfaY, dksA, hupA, invE and clpB.
10 . A composition according to claim 9 , wherein the cell is attenuated by deletion or inactivation of at least one aro gene and at least one omp gene.
11 . A composition according to claim 9 , wherein the cell is attenuated by deletion or inactivation of at least one aro gene and the htrA gene.
12 . A composition according to claim 9 , wherein the cell is attenuated by deletion or inactivation of each of aroC, ompF and ompC.
13 . A composition according to claim 1 , wherein the cell does not express one or more of heat stable toxin (ST), heat labile toxin (LT) and EAST 1.
14 . A composition according to claim 13 , wherein the cell is obtainable by a method comprising deletion of all or a part of the ST gene with a suicide vector.
15 . A composition according to claim 13 , wherein the cell is obtainable by a method comprising site-directed deletion or inactivation of the LT gene and/or the EAST 1 gene.
16 . A composition according to claim 1 , wherein the cell does not express an antibiotic resistance gene.
17 . A composition according to claim 1 , wherein the cell further expresses a heterologous antigen in addition to the three or more CS antigens.
18 . A composition according to claim 17 , wherein the heterologous antigen is an E. coli antigen.
19 . A composition according to claim 17 , wherein the heterologous antigen is a non-toxic component or form of LT.
20 . A composition according to claim 19 , wherein the non-toxic component of LT is the B subunit.
21 . A composition according to claim 1 , wherein the cell is obtainable by a method comprising introduction of a polynucleotide encoding a heterologous CS antigen into a bacterial cell.
22 . A composition according to claim 21 , wherein the polynucleotide comprises the operon of the heterologous CS antigen.
23 . A composition according to claim 21 , wherein the method comprises introducing a polynucleotide encoding a regulatory protein into the cell.
24 . A composition according to claim 21 , wherein the heterologous CS antigen coding sequence is carried on a stable plasmid in the cell.
25 . A composition according to claim 21 , wherein the heterologous CS antigen coding sequence is inserted in the bacterial chromosome of the cell.
26 . A composition according to claim 1 , which comprises a bacterial cell as deposited under accession No. 02082969 at the ECACC.
27 . A composition according to claim 1 , which comprises bacterial cells that together express all of CFA/I, CS1, CS2, CS3, CS4, CS5 and CS6, wherein the composition comprises fewer than five bacterial strains.
28 . A composition according to claim 27 , which comprises three bacterial strains.
29 . A composition according to claim 28 , which comprises:
(i) a strain which expresses CS1, CS2 and CS3; (ii) a strain which expresses CS4, CS5 and CS6; and (iii) a strain which expresses CFA/I.
30 . A method that induces an immune response against three or more coli surface (CS) antigens, comprising administering to a mammal a bacterial cell which expresses said three or more CS antigens.
31 . A method according to claim 30 , wherein the cell is an E. coli cell.
32 . A method according to claim 31 , wherein the cell is an enterotoxigenic E. coli (ETEC) cell.
33 . A method according to claim 30 , wherein the CS antigens are ETEC CS antigens selected from CS1, CS2, CS3, CS4, CS5 and CS6.
34 . A method according to claim 30 , wherein the cell expresses CS1, CS2 and CS3.
35 . A method according to claim 30 , wherein the cell expresses CS4, CS5 and CS6.
36 . A method according to claim 30 , wherein the cell expresses CS1, CS3 and CS4.
37 . A method according to claim 30 , wherein the cell is attenuated by deletion or inactivation of a gene.
38 . A method according to claim 37 , wherein the cell is attenuated by deletion or inactivation of one or more of aroA, aroC, aroD, aroE, pur, htrA, ompC, ompF, ompR, cya, crp, phoP, phoQ, surA, rfaY, dksA, hupA, invE and clpB.
39 . A method according to claim 38 , wherein the cell is attenuated by deletion or inactivation of at least one aro gene and at least one omp gene.
40 . A method according to claim 38 , wherein the cell is attenuated by deletion or inactivation of at least one aro gene and the htrA gene.
41 . A method according to claim 38 , wherein the cell is attenuated by deletion or inactivation of each of aroC, ompF and ompC.
42 . A method according to claim 30 , wherein the cell does not express one or more of heat stable toxin (ST), heat labile toxin (LT) and EAST 1.
43 . A method according to claim 42 , wherein the cell is obtainable by a method comprising deletion of all or a part of the ST gene with a suicide vector.
44 . A method according to claim 42 , wherein the cell is obtainable by a method comprising site-directed deletion or inactivation of the LT gene and/or the EAST 1 gene.
45 . A method according to claim 30 , wherein the cell does not express an antibiotic resistance gene.
46 . A method according to claim 30 , wherein the cell further expresses a heterologous antigen in addition to the three or more CS antigens.
47 . A method according to claim 46 , wherein the heterologous antigen is an E. coli antigen.
48 . A method according to claim 46 , wherein the heterologous antigen is a non-toxic component or form of LT.
49 . A method according to claim 48 , wherein the non-toxic component of LT is the B subunit.
50 . A method according to claim 30 , wherein the cell is obtainable by a method comprising introduction of a polynucleotide encoding a heterologous CS antigen into a bacterial cell.
51 . A method according to claim 50 , wherein the polynucleotide comprises the operon of the heterologous CS antigen.
52 . A method according to claim 50 , wherein the method comprises introducing a polynucleotide encoding a regulatory protein into the cell.
53 . A method according to claim 50 , wherein the heterologous CS antigen coding sequence is carried on a stable plasmid in the cell.
54 . A method according to claim 50 , wherein the heterologous CS antigen coding sequence is inserted in the bacterial chromosome of the cell.
55 . A method according to claim 30 , wherein the bacterial cell is as deposited under accession No. 02082969 at the ECACC.
56 . A method according to claim 30 , which comprises administering bacterial cells that together express all of CFA/I, CS1, CS2, CS3, CS4, CS5 and CS6, wherein fewer than five bacterial strains are administered.
57 . A method according to claim 56 , which comprises administering three bacterial strains.
58 . A method according to claim 56 , which comprises administering:
(i) a strain which expresses CS1, CS2 and CS3; (ii) a strain which expresses CS4, CS5 and CS6; and (iii) a strain which expresses CFA/I.Cited by (0)
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