Glycoconjugate vaccines for use in immune-compromised populations

Abstract

Staphylococcal and Enterrococcal glycoconjugate vaccines are disclosed for use in preventing or treating bacterial infection in an immune-compromised individual. Such vaccines contain an immunocarrier and a conjugate of a polysaccharide or glycopeptide surface antigen from a clinically-significant bacterial strain. The vaccines can be used for active protection in immune-compromised individuals who are to be subjected to conditions that place them at immediate risk of developing a bacterial infection, as would be case in the context of a catheterization or a surgical procedure.

What is claimed is:  
     
         1 . A method of protecting an immune-compromised human from at least one of Staphylococcal and Enterococcal bacterial infection, comprising administering a vaccine comprising a glycoconjugate of a polysaccharide or glycopeptide bacterial surface antigen and an immunocarrier to an immune-compromised human, wherein said vaccine comprises: 
 (a) glycoconjugates of both Type 5 and Type 8 polysaccharide antigens of  S. aureus,      (b) a glycoconjugate of a negatively-charged Staphylococcal polysaccharide antigen that comprises β-linked hexosamine as a major carbohydrate component and contains no O-acetyl groups,    (c) a glycoconjugate of Staphylococcal glycopeptide antigen that comprises amino acids and a N-acetylated hexosamine in an α configuration, that contains no O-acetyl groups, and that contains no hexose,    (d) a glycoconjugate of an acidic Staphylococcal polysaccharide antigen that is obtained from an isolate of  S. epidermidis  that agglutinates antisera to ATCC 55254,    (e) a glycoconjugate of an  E. faecalis  antigen that comprises 2-acetamido-2-deoxy-glucose and rhamnose in a 1:2 molar ratio,    (f) a glycoconjugate of an  E. faecalis  antigen that comprises a trisaccharide repeat which comprises a 6-deoxy sugar,    (g) a glycoconjugate of an  E. faecium  antigen that comprises 2-acetamido-2-deoxy-galactose and galactose in a 2:1 molar ratio,    (h) a glycoconjugate of an  E. faecium  antigen that reacts with antibodies to ATCC 202016, or    (i) a glycoconjugate of an  E. faecium  antigen that reacts with antibodies to ATCC 202017.    
     
     
         2 . A method according to  claim 1 , wherein said vaccine comprises a conjugate of at least one of Type 5 and Type 8 polysaccharide antigen of  S. aureus.    
     
     
         3 . A method according to  claim 1 , wherein said vaccine comprises conjugates of both Type 5 and Type 8 polysaccharide antigen of  S. aureus.    
     
     
         4 . A method according to  claim 1 , wherein said vaccine comprises a polysaccharide antigen that comprises μ-linked hexosamine, contains no O-acetyl groups, and specifically binds with antibodies to  Staphylococcus aureus  Type 336 deposited under ATCC 55804.  
     
     
         5 . A method according to  claim 4 , wherein said vaccine additionally comprises conjugates of Type 5 and Type 8 polysaccharide antigen of  S. aureus.    
     
     
         6 . A method according to  claim 1 , wherein said vaccine comprises an acidic polysaccharide antigen that is obtained from an isolate of  S. epidermidis  that agglutinates antisera to ATCC 55254.  
     
     
         7 . A method according to  claim 1 , wherein said vaccine comprises a Staphylococcal glycopeptide antigen that comprises amino acids and a N-acetylated hexosamine in an α configuration, that contains no O-acetyl groups and that contains no hexose.  
     
     
         8 . A method according to  claim 1 , wherein said polysaccharide conjugate vaccine comprises an  E. faecalis  antigen that comprises 2-acetamido-2-deoxy-glucose and rhamnose in a 1:2 molar ratio.  
     
     
         9 . A method according to  claim 1 , wherein said polysaccharide conjugate vaccine comprises an  E. faecalis  antigen that comprises a trisaccharide repeat which comprises a 6-deoxy sugar.  
     
     
         10 . A method according to  claim 1 , wherein said polysaccharide conjugate vaccine comprises an  E. faecium  antigen that comprises 2-acetamido-2-deoxy-galactose and galactose in a 2:1 molar ratio.  
     
     
         11 . A method according to  claim 1 , wherein said bacterial surface antigen is a capsular polysaccharide antigen.  
     
     
         12 . A method according to  claim 1 , wherein said bacterial surface antigen is a teichoic acid antigen  
     
     
         13 . A method according to  claim 1 , wherein said bacterial surface antigen is a glycopeptide antigen.  
     
     
         14 . A method according to  claim 1 , wherein said immune-compromised human is selected from the group consisting of end stage renal disease (ESRD) patients; cancer patients on immunosuppressive therapy, AIDS patients, diabetic patients, neonates, the elderly in extended care facilities, patients with autoimmune disease on immunosuppressive therapy, transplant patients, patients with invasive surgical procedures, burn patients and other patients in acute care settings.  
     
     
         15 . A method according to  claim 1 , wherein said immune-compromised human suffers from end stage renal disease.  
     
     
         16 . A method according to  claim 1 , wherein said immune-compromised human is a neonate.  
     
     
         17 . A method according to  claim 1 , wherein said immunocarrier is diphtheria toxoid, tetanus toxoid, recombinantly produced, genetically detoxified variants thereof or a recombinantly-produced, non-toxic mutant of  Pseudomonas aeruginosa  exotoxin A or Staphylococcal exotoxin or toxoid.  
     
     
         18 . A method according to  claim 1 , wherein said vaccine additionally comprises an adjuvant or immunostimulant.  
     
     
         19 . A method according to  claim 1 , wherein said vaccine additionally comprises a β-glucan or granulocyte colony stimulating factor.