Compositions and methods related to antibodies that neutralize coagulase activity during staphylococcus aureus disease

Abstract

Embodiments concern methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. Aspects include methods and compositions for providing a passive immune response against the bacteria. In certain embodiments, the methods and compositions involve an antibody that binds Coagulase (Coa). Further aspects relate to immunogenic compositions comprising at least one Staphylococcal coagulase R Domain, wherein the R Domain is 80% identical in sequence to a R Domain.

1 - 29 . (canceled) 
     
     
         30 . An antibody or polypeptide comprising:
 i) a VL domain comprising a CDR1, CDR2, and CDR3 that is least 85% identical to SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively, and/or a VH domain comprising a CDR1, CDR2, and CDR3 that is least 85% identical to SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, respectively; or   ii) a VL domain comprising a CDR1, CDR2, and CDR3 that is least 85% identical to SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20, respectively, and/or a VH domain comprising a CDR1, CDR2, and CDR3 that is least 85% identical to SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17, respectively.   
     
     
         31 . (canceled) 
     
     
         32 . The antibody or polypeptide of  claim 30 , wherein the antibody or polypeptide comprises:
 i) a VL domain comprising a CDR1, CDR2, and CDR3 comprising SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively, and a VH domain comprising a CDR1, CDR2, and CDR3 comprising SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, respectively; or   ii) a VL domain comprising a CDR1, CDR2, and CDR3 comprising SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20, respectively, and a VH domain comprising a CDR1, CDR2, and CDR3 comprising SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17, respectively.   
     
     
         33 . (canceled) 
     
     
         34 . The antibody or polypeptide of  claim 30 , wherein the polypeptide comprises a humanized or chimeric antibody. 
     
     
         35 . The antibody or polypeptide of  claim 30 , wherein the polypeptide has an association constant for a Staphylococcal Coa polypeptide of between about 0.1 and 20 nM −1 , 0.5 and 10 nM −1 , or 1.0 and 10 nM −1  as measured by ELISA. 
     
     
         36 . The antibody or polypeptide of  claim 30 , wherein the polypeptide is operatively coupled to a recombinant polypeptide that specifically binds to a second Staphylococcal protein. 
     
     
         37 . The antibody or polypeptide of  claim 30 , wherein the polypeptide is an antibody comprising (a) a heavy chain comprising said VH region, and a human hinge, CH1, CH2, and CH3 regions from an IgG1, IgG2, IgG3 or IgG4 subtype; and (b) a light chain comprising said VL region, and either a human kappa CL or human lambda CL. 
     
     
         38 . A pharmaceutical composition comprising the antibody or polypeptide of  claim 30 . 
     
     
         39 . The pharmaceutical composition of  claim 38 , comprising a single unit dose of the antibody or polypeptide in a sealed container. 
     
     
         40 . The pharmaceutical composition of  claim 38 , comprising at least a second anti-bacterial agent and optionally wherein the second anti-bacterial agent is an antibiotic, a Staphylococcal vaccine composition, or a polypeptide that specifically binds to a second Staphylococcal protein. 
     
     
         41 . One or more polynucleotide(s) comprising a nucleic acid sequence encoding an antibody or polypeptide according to  claim 30 . 
     
     
         42 . An expression vector comprising a nucleic acid sequence encoding an antibody or polypeptide according to  claim 30  operably linked to an expression control sequence. 
     
     
         43 . A host cell comprising the expression vector of  claim 42 . 
     
     
         44 . A method of manufacturing the antibody or polypeptide of  claim 30  comprising expressing one or more polynucleotides encoding the polypeptide in a host cell, wherein the one or more polynucleotides are operably linked to an expression control sequence. 
     
     
         45 . A method of treating or inhibiting a  Staphylococcus  infection in a subject determined to have or be at risk for  Staphylococcus  infection comprising administering to the subject an effective amount of the composition of the antibody or polypeptide of  claim 30  to the subject. 
     
     
         46 - 58 . (canceled)