Use of antibodies to block the effects of Gram-positive bacteria and mycobacteria

Abstract

The present invention concerns a method of treating bacteremia, sepsis and other forms of toxemia caused by Gram-positive bacteria and mycobacteria comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

1 . A method of ameliorating one or more symptoms of Gram positive bacterial or mycobacterial sepsis in a subject comprising administering to the subject a therapeutically effective amount of an antibody having the same immunoreactivity as an antibody produced by ATCC Accession No. HB11364 (28C5) or an immunoreactive fragment thereof.  
     
     
         2 . The method of  claim 1 , wherein the antibody is the antibody produced by ATCC Accession No. HB11364 (28C5).  
     
     
         3 . The method of  claim 1 , wherein the antibody is comprised of F(ab′) 2  portions.  
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount is 0.1 to 20 milligrams per kilogram body weight per day.  
     
     
         5 . The method of  claim 1 , wherein the method further comprises administering to said patient a bactericidal amount of an antibiotic.  
     
     
         6 . The method of  claim 5 , wherein said antibiotic is an anti-bacterial agent effective against Gram-positive bacteria.  
     
     
         7 . The method of  claim 1  wherein the method further comprises administering to the subject a TNF blood concentration-reducing amount of an anti-TNF antibody.  
     
     
         8 . The method of  claim 1  wherein the subject displays symptoms of one or more of the following: adult respiratory distress syndrome, disseminated intravascular coagulation, renal failure and hepatic failure.  
     
     
         9 . A method of ameliorating Gram positive bacterial or my cobacterial sepsis in a subject comprising administering to the subject a therapeutically effective amount of an antibody having the same immunoreactivity as an antibody produced by ATCC Accession No. HB44 (63D3) or an immunoreactive fragment thereof.  
     
     
         10 . The method of  claim 9 , wherein the antibody is the antibody produced by ATCC Accession No. HB44 (63D3).  
     
     
         11 . The method of  claim 9 , wherein said monoclonal antibody is comprised of F(ab′) 2  portions of anti-CD14 antibody molecules.  
     
     
         12 . The method of  claim 9  wherein said therapeutically effective amount is 0.1 to 20 milligrams per kilogram body weight per day.  
     
     
         13 . The method of  claim 9  wherein said method further comprises substantially simultaneously administering to said patient a bactericidal amount of an antibiotic.  
     
     
         14 . The method of  claim 13  wherein said antibiotic is an anti-bacterial agent effective against Gram-positive bacteria.  
     
     
         15 . The method of  claim 9  wherein the method further comprises administering to the subject patient a TNF blood concentration-reducing amount of an anti-TNF antibody.  
     
     
         16 . The method of  claim 9  wherein the subject displays symptoms of one or more of the following: adult respiratory distress syndrome, disseminated intravascular coagulation, renal failure and hepatic failure.  
     
     
         17 . A method of ameliorating one or more symptoms of Gram positive bacterial or mycobacterial sepsis in a subject comprising administering to the subject, a therapeutically effective amount of an antibody that inhibits binding of Gram-positive toxigenic cell wall components to CD14, and inhibits secretion of tumor necrosis factor by cells of the monocyte macrophage lineage, thereby treating the sepsis.  
     
     
         18 . The method of  claim 17  wherein the antibody is a monoclonal antibody that competitively inhibits the binding of the toxigenic cell wall components to CD14.  
     
     
         19 . The method of  claim 17  wherein the antibody is produced by hybridoma ATCC HB44 or ATCC HB11364 or a host cell containing a polynucleotide encoding a 63D3 or 28C5 antibody.  
     
     
         20 . The method of  claim 17  wherein the Gram-positive bacteria is  Staphylococcus aureus.    
     
     
         21 . The method of  claim 17  wherein the Gram-positive bacteria is selected from the group consisting of Group A and Group B Streptococci.  
     
     
         22 . The method of  claim 17  wherein the Gram-positive bacteria is  Streptococcus pneumoniae.    
     
     
         23 . The method of  claim 17  wherein the mycobacterium is  Mycobacterium tuberculosis.