Vaccines against group neisseria meningitidis and meningococcal combinations thereof
This invention relates to modified meningococcal Y polysaccharides (GYMP), conjugates comprising the modified polysaccharides and a carrier, vaccines for the immunisation of warm-blooded animals, including humans, against Group Y Neisseria meningitidis , and to methods for producing these modified polysaccharides, conjugates and vaccines.
1 . An immunogenic conjugate comprising group Y meningococcal polysaccharide covalently coupled to polymeric carrier, including O-deacetylated O-acetyl-positive group Y meningococcal polysaccharide or a fragment thereof, wherein the degree of de-O-acetylation is greater than 80%, for use as a vaccine against N. meningitidis infection.
2 . An immunogenic conjugate of claim 1 , characterized in the degree of de-O-acetylation is 100%.
3 . A polysaccharide according to claim 1 with a Molecular weight average of one selected from the group consisting of 10 kDa, 50 kDa and 150 kDa.
4 . A polysaccharide according to claim 1 or claim 2 that has been fragmented and wherein the size of the fragment contains between 5 repeating units (ca 2.5 kDa) and 200 repeating units (ca 100 kDa).
5 . A polysaccharide according to claim 1 or claim 2 that has been fragmented and wherin the size of the fragment contains between 20 repeating units (ca 10 kDa) and 40 repeating units (ca 20 kDa).
6 . A conjugate product comprising a de-O-acetylated meningococcal Y polysaccharide conjugated to a carrier protein.
7 . A conjugate product according to claim 4 , wherein the carrier protein is a bacterial toxin or toxoid.
8 . A conjugate product according to claim 5 , wherein the bacteria toxin or toxoid is selected from the group consisting of diphtheria, tetanus, pseudomonas, staphylococcus, streptococcus , pertussis and Escherichia coli toxin or toxoid.
9 . A conjugate product according to claim 6 , wherein the bacterial toxin or toxoid is tetanus toxin or toxoid.
10 . A conjugate product, wherein the modified meningococcal Y polysaccharide is as defined in claim 2 .
11 . A vaccine comprising a conjugate product as defined in claim 4 .
12 . A vaccine according to claim 9 , wherein the bacterial toxin or toxoid is selected from the group consisting of diphtheria, tetanus, pseudomonas, staphylococcus, streptococcus , meningococcal porin B, pertussis and Escherichia coli toxin or toxoid.
13 . A vaccine according to claim 10 , wherein the bacterial toxin or toxoid is tetanus toxin or toxoid.
14 . A vaccine according to claim 1 , which comprises an adjuvant.
15 . A vaccine according to claim 12 , wherein the adjuvant is aluminum hydroxide.
16 . A vaccine according to claim 9 , which is adapted for administration by injection.
17 . A vaccine according to claim 9 , wherein the conjugated material comprises a polysaccharide as defined in claim 2 .
18 . The use of a modified polysaccharide as defined in claim 1 in the manufacture of a vaccine for use in meningitidis against Group Y Neisseria meningitidis.
19 . The use of a conjugated material as defined in claim 4 in the manufacture of a vaccine for use in meningitidis against Group Y Neisseria meningitidis.
20 . A process for the manufacture of a vaccine for use in immunisation against Group Y Neisseria meningitidis , which process comprises providing a modified polysaccharide as defined in claim 1 and optionally mixing it with one or more of a pharmaceutically acceptable carrier medium, diluent or adjuvant.
21 . A process for the manufacture of a vaccine for use in immunisation against Group Y Neisseria meningitidis , which process comprises providing a conjugated material as defined in claim 4 and optionally mixing it with one or more of a pharmaceutically acceptable carrier medium, diluent or adjuvant.
22 . The use of a vaccine as defined in claim 9 for meningitidis against Group Y Neisseria meningitidis.
23 . A process for vaccinating a warm-blooded animal against Group Y Neisseria meningitidis , which process comprises administering a vaccine as defined in claim 9 to the animal.
24 . A process for the preparation of a modified meningococcal Y polysaccharide, which process comprises subjecting a meningococcal Y polysaccharide to base hydrolysis such that the meningococcal Y polysaccharide is at least in part de-O-acetylated.
25 . A process for the preparation of a modified meningococcal Y polysaccharide, which process comprises subjecting a meningococcal Y polysaccharide to acid hydrolysis such that the meningococcal Y polysaccharide is fragmented.
26 . A process for the preparation of a modified meningococcal Y polysaccharide fragment having a molecular weight of from 10 to 20 kDa, which process comprises:
(a) providing an at least partially purified meningococcal Y polysaccharide;
(b) base hydrolysis of the polysaccharide;
(c) acid hydrolysis of the product of step (a); and optionally
(d) re-N-acetylating of the product of step (b).
27 . A process for producing a conjugated product as defined in claim 4 , which process comprises contacting a modified meningococcal Y polysaccharide with a carrier protein, optionally in the presence of a coupling agent.
28 . A combination meningococcal conjugate vaccine including de-OAc forms of group Y, group C and group W135 meningococcal polysaccharides for prevention of meningococcal Y, C and W135 disease.