Methods and Compositions Related to Immunizing Against Staphylococcal Lung Diseases and Conditions

Abstract

Embodiments of the invention include methods and compositions useful in a vaccination strategy capable of neutralizing Hla to provide immunoprotection against S. aureus pneumonia. In certain aspects the invention includes a Hla with reduced toxicity, represented by a recombinant mutant form of Hla (HlaH35L) in which histidine 35 is converted to leucine, which can be used to abrogate the productive assembly of the toxin and protect a subject from staphylococcal pneumonia.

1 .- 76 . (canceled) 
     
     
         77 . An isolated antibody that specifically binds an epitope contained within the first 50 amino acids of a mature Hla toxin, wherein the isolated antibody does not detectably bind a L78-D127 Hla toxin fragment based on a Western blot assay, and wherein the isolated antibody is a humanized antibody, a chimeric antibody, a bispecific antibody, a recombinant antibody, a single chain antibody, an scFv, or an engineered antibody. 
     
     
         78 . The isolated antibody of  claim 77 , wherein the Hla toxin is from  Staphylococcus aureus.    
     
     
         79 . The isolated antibody of  claim 77 , wherein the Hla toxin is an H35L variant. 
     
     
         80 . The isolated antibody of  claim 77 , wherein the isolated antibody competes for binding to a mature Hla toxin with supernatant from hybridoma 7B8.35 (ATCC Accession Number PTA-121360). 
     
     
         81 . The isolated antibody of  claim 77 , wherein the isolated antibody competes for binding to a mature Hla toxin with supernatant from hybridoma 1A9.4F9 (ATCC Accession Number PTA-121613). 
     
     
         82 . The isolated antibody of  claim 77 , wherein the isolated antibody has increased binding to an A1-K50 Hla toxin fragment compared to one of the following Hla toxin fragments: Y40-L88, L78-D127, T117-G166, 1156-K205, L195-N244, or M234-N293. 
     
     
         83 . The isolated antibody of  claim 82 , wherein the isolated antibody has increased binding to an A1-K50 Hla toxin fragment compared to the following Hla toxin fragments: Y40-L88, L78-D127, T117-G166, 1156-K205, L195-N244, and M234-N293. 
     
     
         84 . The isolated antibody of  claim 77 , wherein the isolated antibody does not detectably bind a Y40-L88 Hla toxin fragment based on a Western blot assay. 
     
     
         85 . The isolated antibody of  claim 77 , wherein the isolated antibody does not detectably bind a T117-G166 Hla toxin fragment based on a Western blot assay. 
     
     
         86 . The isolated antibody of  claim 77 , wherein the isolated antibody does not detectably bind a 1156-K205 Hla toxin fragment based on a Western blot assay. 
     
     
         87 . The isolated antibody of  claim 77 , wherein the isolated antibody does not detectably bind a L195-N244 Hla toxin fragment based on a Western blot assay. 
     
     
         88 . The isolated antibody of  claim 77 , wherein the isolated antibody does not detectably bind a M234-N293 Hla toxin fragment based on a Western blot assay. 
     
     
         89 . The isolated antibody of  claim 77 , wherein the isolated antibody comprises complementarity determining regions from a mouse antibody. 
     
     
         90 . The isolated antibody of  claim 89 , wherein the mouse antibody is 7B8.35. 
     
     
         91 . The isolated antibody of  claim 89 , wherein the mouse antibody is 1A9.4F9.