Staphylococcal coagulase antigens and methods of their use

Abstract

The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve coagulase Domains 1-2 and variants thereof.

1 . An immunogenic composition comprising at least two different staphylococcal coagulase Domains 1-2, wherein the Domains 1-2 is 80% identical in sequence to a Domains 1-2 in SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37) or SEQUENCE TABLE NO. 2 (SEQ ID NOs: 38-41) and wherein at least one Domain 1-2 is comprised in a less than full-length coagulase protein. 
     
     
         2 . The composition of  claim 1 , wherein the less than full-length coagulase protein lacks all or part of a L or R Domain segment. 
     
     
         3 . The composition of  claim 1 , wherein the less than full-length coagulase protein lacks all or part of a L or F Domain segment. 
     
     
         4 . The composition of any of  claims 1  to  3 , wherein one of the Domains 1-2 is from a  S. aureus  Newman, 85/2082, MW2, MSSA476, N315, Mu50, MRSA252, CowanI, WIS or USA300 strain. 
     
     
         5 . The composition of any of  claims 1  to  4 , wherein one of the Domains 1-2 is a Coa Domains 1-2 at least 80% identical in sequence to a SEQ ID NO identified in SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37). 
     
     
         6 . The composition of any of  claims 1  to  5 , wherein one of the Domains 1-2 is a vWbp Domains 1-2 at least 80% identical in sequence to a SEQ ID NO identified in SEQUENCE TABLE NO. 2 (SEQ ID NOs: 38-41). 
     
     
         7 . The composition of any of  claims 1  to  6 , wherein the Domains 1-2 are at least 85%, 90% or 95% identical to an amino acid sequence of SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37) or 2 (SEQ ID NOs: 38-41). 
     
     
         8 . The composition of any of  claims 1  to  7 , wherein one of the Domains 1-2 is a vWbp Domains 1-2 from a  S. aureus  N315 or USA300. 
     
     
         9 . The composition of any of  claims 1  to  8 , wherein one of the Domains 1-2 is a Coa Domains 1-2 and comprises a L or R Domain from a staphylococcal Coa protein. 
     
     
         10 . The composition of any of  claims 1  to  9 , wherein one of the Domains 1-2 is a vWbp Domains 1-2 and comprises an L or Fgb domain from a staphylococcal vWbp protein. 
     
     
         11 . The composition of claim any of  claims 1  to  10 , comprising at least three, four or five different staphylococcal coagulase Domains 1-2. 
     
     
         12 . The composition of  claim 11 , comprising at least four different staphylococcal coagulase Domains 1-2 wherein the different Domains 1-2 are staphylococcal Coa Domains 1-2 from strains MRSA252, MW2, N315 and USA300. 
     
     
         13 . The composition of any of  claims 1  to  12 , wherein the at least two different staphylococcal coagulase Domains 1-2 are comprised in a fusion protein. 
     
     
         14 . The composition of any of  claims 1  to  13 , further comprising one or more additional staphylococcal antigen(s). 
     
     
         15 . The composition of  claim 14 , wherein the additional staphylococcal antigen(s) is Emp, EsxA, EsxB, EsaC, Eap, Ebh, EsaB, Coa, vWbp, vWh, Hla, SdrC, SdrD, SdrE, IsdA, IsdB, IsdC, ClfA, ClfB, SasF and/or a nontoxigenic SpA. 
     
     
         16 . The composition of any of  claims 1  to  15 , further comprising an adjuvant. 
     
     
         17 . A recombinant polypeptide comprising at least two different staphylococcal coagulase Domains 1-2 wherein the sequences of the Domains 1-2 are at least 80% identical in sequence to a SEQ ID NO in SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37) or SEQUENCE TABLE 2 (SEQ ID NOs: 38-41). 
     
     
         18 . A polynucleotide molecule comprising a nucleic acid sequence encoding a recombinant polypeptide of  claim 17 . 
     
     
         19 . An expression vector comprising a nucleic acid sequence encoding a recombinant polypeptide of  claim 17  operably linked to an expression control sequence. 
     
     
         20 . A host cell comprising the expression vector of  claim 19 . 
     
     
         21 . A method for treating or preventing a staphylococcal infection in a subject comprising administering an effective amount of a composition of any of  claims 1  to  16 , a recombinant polypeptide of  claim 17  or an expression vector of  claim 19 . 
     
     
         22 . The method of  claim 21 , wherein the subject is a human 
     
     
         23 . The method of  claim 21  or  22 , wherein the subject is treated based on a test for staphyloccal infection. 
     
     
         24 . The method of any of  claims 21  to  23 , wherein the composition or polypeptide is administered multiple time. 
     
     
         25 . The method of any of  claims 21  to  24 , wherein the composition or polypeptide is administered intravenously, intramuscularly, intravascularly, intratracheally, intrathecally, intraocularly, intraperitoneally, topically, orally, by injection, by infusion, or by bolus. 
     
     
         26 . The method of any of  claims 21  to  25 , wherein the composition or polypeptide is administered in a liquid, as a solid, as a gel, tablet, pill, semi-solid, cream, ointment, pessiary, suppository. 
     
     
         27 . The method of any of  claims 21  to  26 , further comprising administering one or more antibiotics to the subject. 
     
     
         28 . The method of any of  claims 21  to  27 , wherein the infection is a drug-resistant infection. 
     
     
         29 . The method of  claim 28 , wherein the drug-resistant infection is methicillin-resistant. 
     
     
         30 . The method of any of  claims 21  to  29  further comprising identifying the subject as having a Staphylococcal infection. 
     
     
         31 . The method of any of  claims 21  to  30 , wherein the patient is administered the composition or polypeptide within 1 week of being determined to have a Staphyloccal infection. 
     
     
         32 . The method of any of  claims 21  to  31 , wherein the subject is immune deficient, is immunocompromised, is hospitalized, is undergoing an invasive medical procedure, has a repiratory infection, is infected with influenza virus or is on a respirator. 
     
     
         33 . The method of any of  claims 21  to  32 , further comprising testing the subject for a response to the composition or the polypeptide. 
     
     
         34 . The method of any of  claims 21  to  32 , wherein the subject exhibits a skin abscess, a boil, or a furuncle. 
     
     
         35 . A method of manufacturing an immunogenic composition comprising mixing at least two different staphylococcal coagulase Domains 1-2, wherein the sequences of the Domains 1-2 are 80% identical to a Domain 1-2 sequence in SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37) or 2 (SEQ ID NOs: 38-41) and wherein at least one Domain 1-2 is comprised in a less than full-length coagulase protein. 
     
     
         36 . A composition for use in treating or preventing a staphylococcal infection comprising at least two different staphylococcal coagulase Domains 1-2 at least 80% identical in sequence to a SEQ ID NO in SEQUENCE TABLE NO. 1 (SEQ ID NOs: 33-37) or SEQUENCE TABLE NO. 2 (SEQ ID NOs: 38-41) and wherein at least one Domain 1-2 is comprised in a less than full-length coagulase protein. 
     
     
         37 . An immunogenic composition comprising at least two different staphylococcal coagulase Domains 1-2 from a staphylococcal Coa or vWbp protein, wherein at least one Domain 1-2 is comprised in a less than full-length coagulase protein.