Modified streptococcal polysaccharides and uses thereof
Modified streptococcal polysaccharides and methods of using the modified polysaccharides are provided herein.
1. An antigenic composition comprising a purified desialylated group B streptococcus (GBS) type V polysaccharide, covalently linked to a polypeptide carrier moiety that facilitates T cell-dependent antibody responses to GBS type V polysaccharide, wherein the antigenic composition induces median serum IgG levels specific for native GBS type V polysaccharide higher than median serum IgM levels specific for native GBS type V polysaccharide when two doses are administered to a monkey.
2. The antigenic composition of claim 1 , wherein the monkey lacks IgM antibodies specific for the native GBS type V polysaccharide prior to the administration of the first dose.
3. The antigenic composition of claim 2 , wherein the antigenic composition induces the median serum IgG levels specific for the native GBS type V polysaccharide of approximately 10 μg/mL when the two doses are administered to the monkey.
4. The antigenic composition of claim 1 , wherein the desialylated GBS type V polysaccharide is obtained by removing sidechain terminal sialic acid residues from a purified native GBS type V polysaccharide.
5. The antigenic composition of claim 4 , wherein the desialylated GBS type V polysaccharide is obtained by treating the purified native GBS type V polysaccharide with 0.1 M sulfuric acid at 80° C. for 60 minutes.
6. The antigenic composition of claim 1 , wherein the polypeptide carrier moiety is a bacterial polypeptide.
7. The antigenic composition of claim 6 , wherein the bacterial polypeptide is a cell-surface or secreted polypeptide.
8. The antigenic composition of claim 1 , wherein the polypeptide carrier moiety is a bacterial toxin or a bacterial toxoid.
9. The antigenic composition of claim 1 , wherein the polypeptide carrier moiety is a tetanus toxoid.
10. The antigenic composition of claim 1 ,wherein the polypeptide carrier moiety is a diphtheria toxoid.
11. The antigenic composition of claim 1 , wherein the polypeptide carrier moiety is diphtheria mutant protein cross-reactive material (CRM 197).
12. The antigenic composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier.
13. The antigenic composition of claim 1 , wherein the composition further comprises an adjuvant.
14. The antigenic composition of claim 13 , wherein the adjuvant is alum.
15. The antigenic composition of claim 4 , wherein the desialylated GBS type V polysaccharide, is obtained by treating the purified native GBS type V polysaccharide with neuraminidase.