Novel immunogens and methods for discovery and screening thereof

Abstract

The present application is generally directed to methods for identifying immunogens from organisms and pathogens, and in particular for identifying immunogens which when administered as vaccines elicit a cellular and/or humoral immune response. The present application is also directed to pneumococcal T-cell immunogens, and vaccine compositions comprising one or a combination of pneumococcal immunogens and methods for treating or preventing pneumococcal infections using the vaccines thereof. The present invention also encompasses use of the pneumococcal immunogens for diagnostic purposes to identify a subject with a pneumococcal infection.

1 - 4 . (canceled) 
     
     
         5 . A method for obtaining bacterial T-cell-stimulating immunogens comprising the steps of:
 killing a bacterial culture with an organic solvent;   removing the solvent;   resuspending the killed bacteria in aqueous solution;   removing particulates from the aqueous solution;   
       whereby T-cell immunogens are retained in the aqueous solution. 
     
     
         6 . The method of  claim 5 , further comprising the steps of:
 isolating the proteins within the aqueous solution;   determining the Th17-cell inducing activity of the isolated proteins, in combination or singly.   
     
     
         7 . The method of  claim 5 , wherein said culture is a culture of  Streptococcus pneumoniae.    
     
     
         8 . The method of  claim 5 , wherein said organic solvent is choloroform. 
     
     
         9 . The method of  claim 5 , wherein said immunogen is further prepared as a vaccine that reduces or protects a mammal against pneumococcal colonization. 
     
     
         10 . The method of  claim 9 , wherein said vaccine further comprises an adjuvant. 
     
     
         11 . The method of  claim 10 , wherein said vaccine is administered mucosally. 
     
     
         12 . The method of  claim 5 , wherein said immunogen is at least one of the pneumococcal proteins SP0862, SP1534, and SP2070 or a functional fragment thereof. 
     
     
         13 . A pharmaceutical composition for eliciting an immune response in a mammal comprising pneumococcal proteins SP0862, SP1534, and SP2070. 
     
     
         14 . A pharmaceutical composition for eliciting an immune response in a mammal comprising the T-cell stimulating immunogens prepared by the method of  claim 5 . 
     
     
         15 . A pharmaceutical composition for eliciting an immune response in a mammal comprising a combination of one or more pneumococcal proteins selected from the group consisting of SEQ ID NO: 1-50 or a functional fragment thereof which can elicit a Th-17 T-cell response. 
     
     
         16 . The pharmaceutical composition of  claim 15 , comprising a combination of one or more pneumococcal proteins selected from the group consisting of SP2070 (SEQ ID NO: 10; SEQ ID NO: 11), SP1534 (SEQ ID NO: 28; SEQ ID NO: 29), SP0435 (SEQ ID NO: 44) and SP862 (SEQ ID NO: 8; SEQ ID NO: 9)), SP516 (SEQ ID NO: 43), SP946 (SEQ ID NO: 35), SP1297 (SEQ ID NO: 20), SP1415 (SEQ ID NO: 38), SP1458 (SEQ ID NO: 33), SP1538, SP1572 (SEQ ID NO: 19), and SP1733 (SEQ ID NO: 35) or a functional fragment thereof which can elicit a Th-17 T-cell response. 
     
     
         17 . The pharmaceutical composition of  claim 15 , wherein the combination comprises one or more pneumococcal proteins selected from the group consisting of: SP435 (SEQ ID NO: 44), 534 (SEQ ID NO: 28 and 29), and SP2070 (SEQ ID NO: 10 and 11). 
     
     
         18 . The method of  claim 5 , wherein the organic solvent is removed by sublimation or evaporation.