Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus

Abstract

Polyclonal and monoclonal antibodies which are cross-reactive to both coagulase-positive staphylococcus bacteria, such as S. aureus and to coagulase-negative bacteria, such as S. epidermidis and S. hemolyticus, are provided which can recognize surface proteins from both coagulase-positive and coagulase negative staph bacteria. The antibodies may be generated from surface proteins that have been isolated on the basis of characteristics that may be common between S. aureus and coagulase-negative staphylococci, and these recombinant surface proteins are used to generate the antibodies of the invention. There is also provided vaccines and methods which utilize these proteins and antibodies for the treatment or protection against a wide variety of staphylococcal infections.

1 . An isolated antibody which is capable of binding to a staphylococcal surface protein selected from the group consisting of SEQ ID NOS. 2, 4, 6, 8, 10, 12, 14, 16, 17, 19 and 21.  
     
     
         2 . The antibody according to  claim 1  wherein the antibody is raised against the A domain of the surface protein.  
     
     
         3 . The antibody according to  claim 1 , wherein the antibody is suitable for parenteral, oral, intranasal, subcutaneous, aerosolized or intravenous administration in a human or animal.  
     
     
         4 . The antibody according to  claim 1 , wherein said antibody is a polyclonal antibody.  
     
     
         5 . The antibody according to  claim 1 , wherein said antibody is a monoclonal antibody.  
     
     
         6 . The antibody according to  claim 5  wherein the monoclonal antibody is of a type selected from the group consisting of murine, chimeric, humanized and human monoclonal antibodies.  
     
     
         7 . The antibody according to  claim 5  wherein the antibody is a single chain monoclonal antibody.  
     
     
         8 . The antibody according to  claim 1  which comprises an antibody fragment having the same binding specificity of an antibody which is capable of biding to a staphylococcal surface protein having the sequence selected from the group consisting of SEQ ID NOS. 2, 4, 6, 8, 10, 12, 14, 16, 17, 19 and 21.  
     
     
         9 . The antibody according to  claim 1  that is raised against a protein having an amino acid sequence selected from the group consisting of SEQ ID NOS. 2, 4, 6, 8, 10, 12, 14, 16, 17, 19 and 21.  
     
     
         10 . The antibody according to  claim 1  wherein the surface protein has an amino acid sequence encoded by a nucleic acid sequence selected from the group consisting of nucleic acid sequences SEQ ID NOS. 1, 3, 5, 7, 9, 11, 13, 15, 20 and the nucleic acid sequences coding for the A domain of the Aap protein or degenerates thereof.  
     
     
         11 . Isolated antisera containing an antibody according to  claim 1 .  
     
     
         12 . A diagnostic kit comprising an antibody according to  claim 1  and means for detecting binding by that antibody.  
     
     
         13 . A diagnostic kit according to  claim 12  wherein said means for detecting binding comprises a detectable label that is linked to said antibody.  
     
     
         14 . A method of diagnosing an infection of  S. aureus  comprising adding an antibody according to  claim 1  to a sample suspected of being infected with  S. aureus,  and determining if antibodies have bound to the sample.  
     
     
         15 . A pharmaceutical composition for treating or preventing an infection of  S. aureus  comprising an effective amount of the antibody of  claim 1  and a pharmaceutically acceptable vehicle, carrier or excipient.  
     
     
         16 . A method of treating or preventing an infection of  S. aureus  comprising administering to a human or animal patient an effective amount of an antibody according to  claim 1 .  
     
     
         17 . A method of inducing an immunological response comprising administering to a human or animal an immunogenic amount of an isolated protein selected from the group consisting of the amino acid sequences SEQ ID NOS. 2, 4, 6, 8, 10, 12, 14, 16, 17, 18, 19 and 21.  
     
     
         18 . An isolated antibody according to  claim 1  that has the ability to bind to an amino acid sequence coded by the nucleic acid sequence of SEQ ID NOS. 1, 3, 5, 7, 9, 11, 13, 15, 20 and the nucleic acid sequences coding for the A domain of the Aap protein or degenerates thereof.  
     
     
         19 . An isolated active fragment from the A domain of the DsqA protein.  
     
     
         20 . A composition comprising the isolated antibody according to  claim 1  and a physiologically acceptable antibiotic.  
     
     
         21 . A vaccine for treating or preventing an infection of  S. aureus  comprising an amount of a protein sequence selected from the group consisting of SEQ ID NOS. 2, 4, 6, 8, 10, 12, 14, 16, 17, 18, 19 and 21 in an amount effective to elicit an immune response, and a pharmaceutically acceptable vehicle, carrier or excipient.