Staphylococcal immunotherapeutics via donor selection and donor stimulation

Abstract

A method and composition for the passive immunization of patients infected with or susceptible to infection from Staphylococcus bacteria such as S. aureus and S. epidermidis infection is provided that includes the selection or preparation of a donor plasma pool with high antibody titers to carefully selected Staphylococcus adhesins or MSCRAMMs, or fragments or components thereof, or sequences with substantial homology thereto. The donor plasma pool can be prepared by combining individual blood or blood component samples which have higher than normal titers of antibodies to one or more of the selected adhesins or other proteins that bind to extracellular matrix proteins, or by administering carefully selected proteins or peptides to a host to induce the expression of desired antibodies, and subsequently recovering the enhanced high titer serum or plasma pool from the treated host.

1 . A method of obtaining a human immunoglobulin composition having a higher antibody titer to a staphylococcal clumping factor A (ClfA) adhesin than that found in pooled intravenous immunoglobulin obtained from unselected human donors comprising obtaining blood or plasma samples from human donors, identifying those blood or plasma samples from high-titer donors having the presence of an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors, recovering blood or plasma from the identified high-titer donors, and treating the donor blood or plasma to obtain a human immunoglobulin composition in a purified state that has an antibody titer to ClfA in an amount which is higher than that found in intravenous immunoglobulin obtained from unselected donors.  
     
     
         2 . The method according to  claim 1  wherein donors are identified which have an antibody titer to ClfA in an amount which is 2-fold or greater than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         3 . The method according to  claim 1  wherein donors having a high titer to ClfA are determined by identifying those samples having a high titer of antibodies to the A domain of ClfA.  
     
     
         4 . The method according to  claim 1  further comprising identifying those samples also having an antibody titer to a second staphylococcal adhesin which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         5 . The method according to  claim 4  wherein the second staphylococcal adhesin is an Sdr protein.  
     
     
         6 . The method according to  claim 5  wherein donors having a high titer to the Sdr protein are determined by identifying those samples having a high titer of antibodies to the A domain of the Sdr protein.  
     
     
         7 . The method according to  claim 5  wherein the Sdr protein is selected from the group consisting of SdrF, SdrG, and SdrH.  
     
     
         8 . A human immunoglobulin composition obtained by the method of  claim 1 .  
     
     
         9 . A method of obtaining a human immunoglobulin composition having a higher antibody titer to a staphylococcal ClfA adhesin than that found in pooled intravenous immunoglobulin obtained from unselected human donors comprising administering ClfA to a host donor in an amount sufficient so as to induce an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors, recovering blood or plasma from the host donor, and treating the donor blood or plasma to obtain a human immunoglobulin composition in a purified state that has an antibody titer to ClfA which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         10 . The method according to  claim 9  wherein the host donor is induced to have an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors by administering the A domain of ClfA to the host donor an amount sufficient so as to induce an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         11 . The method according to  claim 9  wherein immunoglobulin is obtained that has an antibody titer to ClfA in an amount which is 2-fold or greater than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         12 . The method according to  claim 9  further comprising administering a second staphylococcal adhesin to a host donor in an amount sufficient so as to induce an antibody titer to the second adhesin in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         13 . The method according to  claim 12  wherein the second staphylococcal adhesin is an Sdr protein.  
     
     
         14 . The method according to  claim 13  wherein the host donor is induced to have an antibody titer to the Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors by administering the A domain of the Sdr protein an amount sufficient so as to induce an antibody titer to the Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         15 . The method according to  claim 13  wherein the Sdr protein is selected from the group consisting of SdrF, SdrG, and SdrH.  
     
     
         16 . A human immunoglobulin composition obtained by the method of  claim 9 .  
     
     
         17 . A method of obtaining a human immunoglobulin composition having a higher than normal antibody titer to a staphylococcal Sdr protein comprising obtaining blood or plasma samples from donors, identifying those blood or plasma samples from high-titer donors having the presence of an antibody titer to a staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors, recovering blood or plasma from the identified high-titer donors, and treating the donor blood or plasma to obtain a human immunoglobulin composition in a purified state that has an antibody titer to a staphylococcal Sdr protein in an amount which is higher than that found in intravenous immunoglobulin obtained from unselected donors.  
     
     
         18 . The method according to  claim 17  wherein donors are identified which have an antibody titer to a staphylococcal Sdr protein in an amount which is 2-fold or greater than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         19 . The method according to  claim 18  wherein donors having a high titer to a staphylococcal Sdr protein are determined by identifying those samples having a high titer of antibodies to the A domain of a staphylococcal Sdr protein.  
     
     
         20 . The method according to  claim 18  further comprising identifying those samples also having an antibody titer to a second adhesin which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         21 . The method according to  claim 20  wherein the second adhesin is also a staphylococcal Sdr protein.  
     
     
         22 . The method according to  claim 21  wherein donors having a high titer to the second staphylococcal Sdr protein are determined by identifying those samples having a high titer of antibodies to the A domain of the second staphylococcal Sdr protein.  
     
     
         23 . A human immunoglobulin composition obtained by the method of  claim 18 .  
     
     
         24 . A method of obtaining a human immunoglobulin composition having a higher than normal antibody titer to a staphylococcal Sdr protein comprising administering a staphylococcal Sdr protein to a host donor in an amount sufficient so as to induce an antibody titer to a staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors, recovering blood or plasma from the host donor, and treating the donor blood or plasma to obtain a human immunoglobulin composition in a purified state that has an antibody titer to a staphylococcal Sdr protein which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         25 . The method according to  claim 24  wherein the host donor is induced to have an antibody titer to a staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors by administering the A domain of a staphylococcal Sdr protein to the host donor in an amount sufficient so as to induce an antibody titer to a staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         26 . The method according to  claim 24  wherein immunoglobulin is obtained that has an antibody titer to a staphylococcal Sdr protein in an amount which is 2-fold or greater than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         27 . The method according to  claim 24  further comprising administering a second adhesin to a host donor in an amount sufficient so as to induce an antibody titer to the second adhesin in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         28 . The method according to  claim 27  wherein the second adhesin is a second staphylococcal Sdr protein.  
     
     
         29 . The method according to  claim 28  wherein the host donor is induced to have an antibody titer to the second staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors by administering the A domain of the second staphylococcal Sdr protein an amount sufficient so as to induce an antibody titer to the second staphylococcal Sdr protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.  
     
     
         30 . A human immunoglobulin composition obtained by the method of  claim 24 .  
     
     
         31 . A method of obtaining an immunoglobulin composition having a higher antibody titer to a staphylococcal clumping factor A (ClfA) adhesin than that found in pooled intravenous immunoglobulin obtained from unselected human donors comprising obtaining blood or plasma samples from human donors, and: 
 (a) identifying those blood or plasma samples from high-titer donors having the presence of an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors and identifying those samples also having an antibody titer to a second staphylococcal adhesin selected from the group consisting of a fibronectin binding protein, a collagen binding protein, a fibrinogen binding protein, an elastin binding protein and an MHC-II analogous protein in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors.    (b) recovering blood or plasma from the identified high-titer donors, and    (c) treating the recovered blood or plasma to obtain immunoglobulin in a purified state that has an antibody titer to ClfA in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors and an antibody titer to the second staphylococcal adhesin in an amount which is higher than that found in pooled intravenous immunoglobulin obtained from unselected donors;    
     
     
         32 . The method according to  claim 31  wherein the second staphylococcal adhesin is selected from the group consisting of proteins fibronectin binding protein A (FnBP-A), fibronectin binding protein B (FnBP-B), clumping factor protein B (ClfB), SdrC, SdrD, SdrE, SdrF, SdrG, SdrH, CNA, and EbpS.  
     
     
         33 . The method of  claim 31  wherein donors having a high titer to the staphylococcal Sdr protein are determined by identifying those samples having a high titer of antibodies to the A domain of the staphylococcal Sdr protein.