Antibodies targeted to fungal cell wall polysaccharides
A compound comprising one or more polysaccharide moieties each independently represented by the formula β(1→4)-[GlcNH—R] n -2,5-anhydromannose, wherein n is a positive integer from 3 to 500, and R is H or an acyl group, is described. The compound can be manufactured by (a) reacting chitosan with an acylating agent sufficient to partially N-acylate the chitosan, yielding a modified chitin/chitosan mixed polymer; and (b) reacting the modified chitin/chitosan mixed polymer with a deaminating agent to cleave the mixed polymer at the unacylated chitosan moieties. The compound can be used to immunize against fungal infection. Antibodies specific to the compound, and the use of such antibodies to protect against fungal infection are also described.
1. A method of immunizing a mammalian subject against a fungal pathogen, comprising administering to the subject an immunogenic amount of a compound, wherein the compound comprises:
one or more polysaccharide moieties, each independently represented by the formula β(1→4)-[GlcNH—R] n -2,5-anhydromannose, wherein n is a positive integer from 3 to 500, R is H or an acyl group, and the one or more polysaccharide moieties are chitin/chitosan mixed polymers;
and an immunogenic carrier protein covalently linked to the one or more polysaccharide moieties at the anhydromannose group of the polysaccharide moieties.
2. The method of claim 1 , wherein n is a positive integer from 3 to 100.
3. The method of claim 2 , wherein n is a positive integer from 6 to 50.
4. The method of claim 1 , wherein the acyl group R is an acetyl group.
5. The method of claim 1 , wherein at least 30% of the acyl groups in the compound are acetyl.
6. The method of claim 1 , wherein the carrier protein is tetanus toxoid.
7. The method of claim 1 , wherein the carrier protein is diphtheria toxoid.
8. The method of claim 1 , wherein the carrier protein is a fungal protein virulence factor.
9. The method of claim 1 , wherein the compound further comprises one or more linear β-mannan or glucan epitopes covalently linked to the carrier protein.
10. The method of claim 9 , wherein the β-mannan is a β-1,2-mannose tetrasaccharide.
11. The method of claim 9 , wherein one of the one or more glucan epitopes is a linear α-1,3-glucan epitope.
12. The method of claim 9 , wherein one of the one or more glucan epitopes is a linear β-1,3-glucan epitope.
13. The method of claim 1 , wherein the carrier protein is covalently linked to the one or more polysaccharide moieties via one or more immunogenic scaffold moieties.
14. The method of claim 13 , wherein each of the scaffold moieties is selected from the group consisting of a polysaccharide, a peptidoglycan, a polypeptide, and a polyglycerol.
15. The method of claim 13 , wherein the scaffold is linear.
16. The method of claim 13 , wherein the scaffold is dendrimeric.
17. The method of claim 13 , wherein the compound further comprises one or more linear β-mannan or glucan epitopes covalently linked to the carrier protein or the scaffold.
18. The method of claim 17 , wherein the β-mannan is a β-1,2-mannose tetrasaccharide.
19. The method of claim 17 , wherein one of the one or more glucan epitopes is a linear α-1,3-glucan epitope.
20. The method of claim 17 , wherein one of the one or more glucan epitopes is a linear β-1,3-glucan epitope.