Bacterial polysaccharide-conjugated carrier proteins and use thereof

Abstract

Immunogenic compositions that include a bacterial capsular polysaccharide conjugated to a carrier protein are described. In some embodiments, the bacterial capsular polysaccharide is a Neisseria meningitidis capsular polysaccharide. The carrier protein includes an N. meningitidis factor H binding protein (fHbp) linked to cholera toxin subunit B (CTB). Administration of the immunogenic compositions elicits an immune response that includes production of meningococcal polysaccharide-specific and fHbP-specific antibodies. Use of the immunogenic compositions as meningococcal vaccines is also described.

1 . An immunogenic composition, comprising a bacterial capsular polysaccharide conjugated to a protein, wherein the protein comprises:
 a  N. meningitidis  factor H binding protein (fHbp); fused to a linking domain; and   a cholera toxin subunit B (CTB), wherein the fHbp is covalently or non-covalently linked to the CTB.   
     
     
         2 . The method of  claim 1 , wherein the capsular polysaccharide is a  Streptococcus pneumonia  polysaccharide, a  Haemophilus influenzae  polysaccharide, a  Salmonella typhi  polysaccharide, or a Group B  Streptococcus agalactiae  polysaccharide. 
     
     
         3 . The immunogenic composition of  claim 1 , wherein the fHbp-linking domain is non-covalently linked to CTB. 
     
     
         4 . The immunogenic composition of  claim 1 , wherein the amino acid sequence of the fHbp is at least 95% identical to SEQ ID NO: 1. 
     
     
         5 . The immunogenic composition of  claim 4 , wherein the amino acid sequence of the fHbp comprises SEQ ID NO: 1. 
     
     
         6 . The immunogenic composition of  claim 1 , wherein the linking domain comprises a cholera toxin subunit A2 domain. 
     
     
         7 . The immunogenic composition of  claim 6 , wherein the amino acid sequence of the A2 domain is at least 95% identical to SEQ ID NO: 2. 
     
     
         8 . The immunogenic composition of  claim 7 , wherein the amino acid sequence of the A2 domain comprises or consists of SEQ ID NO: 2. 
     
     
         9 . The immunogenic composition of  claim 1 , wherein the amino acid sequence of the CTB is at least 95% identical to SEQ ID NO: 3. 
     
     
         10 . The immunogenic composition of  claim 9 , wherein the amino acid sequence of the CTB comprises or consists of SEQ ID NO: 3. 
     
     
         11 . The immunogenic composition of  claim 1 , further comprising a pharmaceutically acceptable carrier. 
     
     
         12 . The immunogenic composition of  claim 10 , further comprising an adjuvant. 
     
     
         13 . A method of inducing an immune response to a bacterium in a subject, comprising administering to the subject an effective amount of the immunogenic composition of  claim 1 , thereby inducing the immune response to the bacterium. 
     
     
         14 . The method of  claim 13 , wherein the immune response is a protective immune response. 
     
     
         15 . The method of  claim 13 , wherein the immune response is a therapeutic immune response. 
     
     
         16 . The method of  claim 13 , wherein the subject is human. 
     
     
         17 . The method of  claim 13 , wherein the bacterium is a  Streptococcus pneumonia  or a  Streptococcus agalactiae.    
     
     
         18 . The method of  claim 13 , wherein the bacterium is a  Salmonella typhi.    
     
     
         19 . The method of  claim 13 , wherein the bacterium is a  Streptococcus agalactiae.