STREPTOCOCCAL GlcNAc-LACKING GLYCOPOLYPEPTIDES, CELL WALL CARBOHYDRATES, STREPTOCOCCUS VACCINES, AND METHODS FOR MAKING AND USING THEM

Abstract

In alternative embodiments, the invention provides vaccines, pharmaceutical compounds and formulations for diagnosing, preventing, treating or ameliorating Group A Streptococcus (GAS), Group C Streptococcus (GCS), or Group A Streptococcus (GGS), infections, or other pathogenic Streptococcus infections. In alternative embodiments, the invention provides compositions such as diagnostic tests, assays, immunoassays and test strips, and methods, for detecting or diagnosing the presence of a Streptococcal infection, e.g., Group A Streptococcus (GAS), Group C Streptococcus (GCS), or Group A Streptococcus (GGS), infections, or other pathogenic Streptococcus infections.

1 : An isolated, synthetic or recombinant Group A  Streptococcus  (GAS) carbohydrate, glycoprotein or glycoconjugate variant/mutant:
 (a) partially lacking, substantially lacking, or completely lacking an immunodominant GlcNac side chain;   (b) partially lacking, substantially lacking, or completely lacking an autoreactive GlcNAc component;   (c) having a polyrhamnose backbone rather than: an immunodominant side chain, an immunodominant GlcNac side chain, or a group A carbohydrate (GAC) antigen, or   (d) comprising any combination of (a) to (c).   
     
     
         2 : An isolated, synthetic or recombinant Group C  Streptococcus  (GCS) carbohydrate, glycoprotein or glycoconjugate variant/mutant:
 (a) partially lacking, substantially lacking, or completely lacking an immunodominant GalNAc-GalNAc side chain;   (b) partially lacking, substantially lacking, or completely lacking an autoreactive GalNAc-GalNAc component;   (c) having a polyrhamnose backbone rather than: an immunodominant GalNAc-GalNAc side chain, or a group C carbohydrate (GCC) antigen, or   (d) comprising any combination of (a) to (c).   
     
     
         3 : An isolated, synthetic or recombinant Group G  Streptococcus  (GGS) carbohydrate, glycoprotein or glycoconjugate variant/mutant:
 (a) partially lacking, substantially lacking, or completely lacking an immunodominant glycan side chain; or,   (b) partially lacking, substantially lacking, or completely lacking an autoreactive glycan component; or,   (c) having a polyrhamnose backbone rather than: an immunodominant glycan side chain, or a group G carbohydrate (GGC) antigen, or   (d) comprising any combination of (a) to (c).   
     
     
         4 : A vaccine, a formulation, a composition or a pharmaceutical composition comprising a carbohydrate, glycoconjugate or glycopeptide selected from the group consisting of:
 (a) an isolated, synthetic or recombinant Group A  Streptococcus  (GAS) carbohydrate, glycoprotein or glycoconjugate variant/mutant:
 (i) partially lacking, substantially lacking, or completely lacking an immunodominant GlcNac side chain; 
 (ii) partially lacking, substantially lacking, or completely lacking an autoreactive GlcNAc component; 
 (iii) having a polyrhamnose backbone rather than: an immunodominant side chain, an immunodominant GlcNac side chain, or a group A carbohydrate (GAC) antigen, or 
 (iv) comprising any combination of (i) to (iii); 
   (b) an isolated, synthetic or recombinant Group G  Streptococcus  (GGS) carbohydrate, glycoprotein or glycoconjugate variant/mutant:
 (i) partially lacking, substantially lacking, or completely lacking an immunodominant glycan side chain; or, 
 (ii) partially lacking, substantially lacking, or completely lacking an autoreactive glycan component; or, 
 (iii) having a polyrhamnose backbone rather than: an immunodominant glycan side chain, or a group G carbohydrate (GGC) antigen, or 
 (iv) comprising any combination of (i) to (iii); 
   (c) an isolated, synthetic or recombinant Group C  Streptococcus  (GCS) carbohydrate variant/mutant:
 (i) partially or completely lacking an immunodominant GalNAc-GalNAc side side chain; 
 (ii) partially or completely lacking an autoreactive GalNAc-GalNAc side component; 
 (iii) having a polyrhamnose backbone rather than: an immunodominant GalNAc-GalNAc side side chain, or a Group C carbohydrate (GCC) antigen; or 
 (iv) comprising any combination of (i) to (iii) 
 partially or completely lacking an immunodominant side chain; or, partially or completely lacking an autoreactive component; or 
 having a polyrhamnose backbone rather than an immunodominant glycan side chain, or a group G carbohydrate (GGS) antigen; 
   (d) the isolated, synthetic or recombinant carbohydrate variant/mutant of (a) and (b);   (e) the isolated, synthetic or recombinant carbohydrate variant/mutant of (a) and (c);   (f) the isolated, synthetic or recombinant carbohydrate variant/mutant of (b) and (c); and   (g) the isolated, synthetic or recombinant carbohydrate variant/mutant of (a), (b) and (c).   
     
     
         5 : The vaccine, formulation, composition or pharmaceutical composition of  claim 4 , further comprising one or more different or additional GAS, GCC and/or GGC protein antigen or antigens. 
     
     
         6 : The vaccine, formulation, composition or pharmaceutical composition of  claim 4 :
 (a) further comprising an adjuvant and/or a pharmaceutically acceptable excipient;   (b) formulated as a liquid, a powder, a liposome, an aerosol, a nanoparticle or a lyophilized, freeze-dried or cryodessicated preparation,   (c) formulated as an emulsion, a lyophilized powder, a spray, a cream, a lotion, a controlled release formulation, a tablet, a pill, a gel, a patch, in an implant or in a spray, or is formulated as an aqueous or a non-aqueous isotonic sterile injection solution, or an aqueous or a non-aqueous sterile suspension; or   (d) formulated as a vaccine or a pharmaceutical for the prevention, amelioration or treatment of strep throat, impetigo, cellulitis, necrotizing fascititis, toxic shock syndrome, or post-streptococcal glomerulonephritis.   
     
     
         7 - 14 . (canceled) 
     
     
         15 : A kit comprising: a vaccine, a formulation, a composition or a pharmaceutical composition of  claim 4 . 
     
     
         16 : An isolated or recombinant antibody, a polyclonal or a monoclonal antibody, or a sera or a hyperimmune serum, wherein the antibody or serum specifically reacts against, or specifically binds to, or is specifically derived against:
 (a) a mutant GAS, GGS or GCS carbohydrate antigen, engineered to partially lack, substantially lack or completely lack an immuno-crossreactive carbohydrate side chain,   (b) a mutant GAS carbohydrate antigen engineered to partially lack, substantially lack or completely lack an immuno-crossreactive GlcNac side chain;   (c) a mutant GCS carbohydrate antigen engineered to partially lack, substantially lack or completely lack an immunodominant GalNac-GalNac side chain; or   (d) any combination or all of (a), (b) and (c).   
     
     
         17 : The isolated or recombinant antibody, polyclonal or a monoclonal antibody, or a sera or a hyperimmune serum of  claim 16 , wherein the antibody or serum is formulated for active or passive immunotherapy in a mammal. 
     
     
         18 : A vaccine or formulation comprising one or more isolated or recombinant antibodies, a polyclonal or a monoclonal antibodies, or a sera or a hyperimmune sera of  claim 16 , wherein the antibodies or sera specifically react against, or specifically bind to, or are specifically derived against one, two or all of:
 (a) a mutant GAS, GGS or GCS carbohydrate antigen, engineered to partially lack, substantially lack or completely lack an immuno-crossreactive carbohydrate side chain,   (b) a mutant GAS carbohydrate antigen engineered to partially lack, substantially lack or completely lack an immuno-crossreactive GlcNac side chain; and/or   (c) a mutant GCS carbohydrate antigen engineered to partially lack, substantially lack or completely lack an immunodominant GalNac-GalNac side chain.   
     
     
         19 : A method for active or passive immunotherapy in a mammal for preventing or ameliorating a GAS, a GGS or a GCS infection in a mammal, a human or a horse, comprising:
 (a) providing the isolated or recombinant antibody, polyclonal or a monoclonal antibody, or hyperimmune serum of  claim 16 ; and   (b) administering a therapeutically or prophylactically effective dose or dosages of the isolated or recombinant antibody, polyclonal or a monoclonal antibody, or the serum or hyperimmune serum, or vaccine or formulation, to the mammal, a human or a horse.   
     
     
         20 : A diagnostic test, an assay, an immunoassay or a test strip, or a bead or latex bead, or an array, a microarray, a biochip, diagnostic chip or chip, for detecting or diagnosing the presence of a Streptococcal infection, comprising or having affixed or attached thereon:
 the isolated or recombinant antibody, polyclonal or a monoclonal antibody, or serum or hyperimmune serum of  claim 16 .   
     
     
         21 : The diagnostic test, assay, immunoassay or test strip, or array, microarray, biochip, diagnostic chip or chip, of  claim 20 , wherein the test or assay comprises a latex agglutination assay or beads, enzyme immunoassay or an optical, liquid or solid phase immunoassay. 
     
     
         22 : A hydrogel, a particle or a magnetic particle for detecting or diagnosing the presence of a Streptococcal infection, comprising or having affixed or attached thereon the isolated or recombinant antibody, polyclonal or a monoclonal antibody, or hyperimmune serum of  claim 16 ,
 wherein optionally the hydrogel, particle or magnetic particle detects the presence of or diagnoses a Streptococcal pharyngitis (“strep throat”), impetigo, cellulitis, necrotizing fascititis, toxic shock syndrome, or post-streptococcal glomerulonephritis, in a human,   wherein optionally the hydrogel, particle or magnetic particle detects the presence of or diagnoses a Streptococcal infection,   wherein optionally the Streptococcal infection is a GAS, a GGS or a GCS infection in a mammal.   
     
     
         23 : An array, a microarray, a biochip, a diagnostic chip or a chip, for detecting or diagnosing the presence of a Streptococcal infection, comprising or having affixed or attached thereon an isolated or a recombinant antibody, polyclonal or a monoclonal antibody, or a serum or a hyperimmune serum of  claim 16 ,
 wherein optionally the biochip, diagnostic chip or chip detects the presence of or diagnoses a Streptococcal pharyngitis (“strep throat”) in a human,   wherein optionally the diagnostic test, assay, immunoassay or test strip detects the presence of or diagnoses a Streptococcal infection,   wherein optionally the Streptococcal infection is a GAS, a GGS or a GCS infection in a mammal.   
     
     
         24 - 25 . (canceled) 
     
     
         26 : The vaccine, formulation, composition or pharmaceutical composition of  claim 4 , wherein the carbohydrate, glycoconjugate or glycopeptide comprises, or is the same as or is derived from: a pathogenic streptococci of a group B  Streptococcus  (GBS), for example, a  Streptococcus agalactiae , or a group G  Streptococcus  (GGS) carbohydrate (GCC) antigen. 
     
     
         27 : The vaccine, formulation, composition or pharmaceutical composition of  claim 4 , wherein the vaccine, formulation, composition or pharmaceutical composition, comprises: a polyrhamnose backbone, or a plurality of polyrhamnose backbones derived from a GAS; GCS; a GBS; a GGS; a GAS and a GCS; a GAS and a GBS; a GAS and a GGS; a GCS and a GBS; a GCS and a GGS; a GBS and a GGS; or a GAS, a GCS, a GBS and a GGS. 
     
     
         28 : The isolated or recombinant antibody, polyclonal or a monoclonal antibody, or a sera or a hyperimmune serum of  claim 16 , wherein the antibody or serum is formulated for treating, ameliorating or for preventing a GAS, GGS or GCS infection in a mammal, a human or a horse. 
     
     
         29 : The method of  claim 19 , wherein the immunotherapy is for the prevention, amelioration or treatment of strep throat, impetigo, cellulitis, necrotizing fascititis, toxic shock syndrome, or post-streptococcal glomerulonephritis. 
     
     
         30 : The diagnostic test, assay, immunoassay, test strip, bead, latex bead, array, microarray, biochip, diagnostic chip or chip, of  claim 20 , wherein:
 (a) the diagnostic test, assay, immunoassay or test strip, or array, microarray, biochip, diagnostic chip or chip, detects the presence of or diagnoses a Streptococcal pharyngitis (“strep throat”) in a human,   (b) the diagnostic test, assay, immunoassay or test strip, or array, microarray, biochip, diagnostic chip or chip, detects the presence of or diagnoses a strep throat, impetigo, cellulitis, necrotizing fascititis, toxic shock syndrome, or post-streptococcal glomerulonephritis,   (c) the diagnostic test, assay, immunoassay or test strip, or array, microarray, biochip, diagnostic chip or chip, detects the presence of or diagnoses a Streptococcal infection, or   (d) the Streptococcal infection is a GAS, a GGS or a GCS infection in a mammal.