Low contaminant compositions
Disclosed are antimicrobial vaccines comprising oligosaccharide β-(1→6)-glucosamine groups.
1. A composition comprising a pharmaceutically acceptable excipient and an effective amount of a conjugate of formula
(A-B) x -C I
where A comprises from 3 to 12 repeating β-(1→6)-glucosamine units or mixtures thereof having the formula:
B is of the formula:
wherein each unit (A-B)- of (A-B) x is attached to C via the amide nitrogen of B indicated at the vertical dashed line of B; and
C is tetanus toxoid;
x is an integer from at least about 10 to about 40;
y is an integer from 1 to 10; and
R is hydrogen or acetyl provided that no more than 40% of the R groups are acetyl;
wherein said composition comprises less than 3 weight percent of detectable impurities having a molecular weight of less than 50,000; and
further wherein said composition comprises monomeric and dimeric toxoid with less than 5 percent of detectable higher oligomers.
2. The composition of claim 1 , wherein R is hydrogen.
3. The composition of claim 2 , wherein y is 3.
4. The composition of claim 3 , wherein x is at least 25.
5. The composition of claim 1 , wherein said composition is maintained at a temperature to inhibit oligomerization of the toxoid.
6. The composition of claim 5 , wherein the composition is maintained at a temperature to not induce denaturation.
7. The composition of claim 1 , wherein said composition comprises no more than about 0.5 weight percent of oligosaccharide-linked contaminants having a particle size of less than 1 micron wherein said weight percent is based on the weight of a vaccine compound.
8. The composition of claim 1 wherein said conjugate is selected from:
where x is 10, y is 2, C is tetanus toxoid.
9. The composition of claim 1 wherein said conjugate is selected from:
where x is 15, y is 3, C is tetanus toxoid.
10. The composition of claim 1 wherein said conjugate is selected from:
where x is 40, y is 3, C is tetanus toxoid.