Composition for Immunization Against Streptococcus Pneumoniae

Abstract

This disclosure relates to a method of preventing or treating a recurrence of acute otitis media in a subject at risk comprising administering a therapeutically effective amount of a composition, at least once to the subject. The composition administered comprises at least one immunogenic polypeptide selected from the group consisting of Streptococcus pneumoniae PhtD, C PhtE, PcpA, LytB and detoxified pneumolysis

1 - 38 . (canceled) 
     
     
         39 . A method comprising administering a therapeutically effective amount of a composition comprising at least one of  Streptococcus pneumoniae  PhtD, PhtE, PcpA, LytB and detoxified pneumolysin, or an immunogenic fragment thereof, at least once to said subject. 
     
     
         40 . The method of  claim 39 , wherein the subject has previously experienced at least one episode of acute otitis media. 
     
     
         41 . The method of  claim 40 , wherein the subject has experienced three or more episodes of acute otitis media within a period of six months or has experienced four or more episodes of acute otitis media within a period of 12 months. 
     
     
         42 . The method of  claim 39 , wherein the subject has or is at risk for developing acute otitis media. 
     
     
         43 . The method of  claim 42 , wherein the subject has acute otitis media. 
     
     
         44 . The method of  claim 39 , wherein administration of the composition elicits or enhances the production of antigen specific CD4+ T-cells. 
     
     
         45 . The method of  claim 44 , wherein administration of composition elicits or enhances the production of antigen specific CD4+ T-cells producing IFN-γ, IL-4, IL-2 and/or IL-17a. 
     
     
         46 . The method of  claim 45 , wherein percentage of antigen specific CD4+ T-cells producing IFN-γ, IL-4, IL-2 and/or IL-17a increases relative to the percentage existing immediately preceding the administration of the composition. 
     
     
         47 . The method of  claim 39 , wherein administration stimulates the production of IFN-γ, IL-2, IL-4 and/or IL-17a cytokines. 
     
     
         48 . The method of  claim 39 , wherein the composition further comprises at least one adjuvant. 
     
     
         49 . The method of  claim 39  wherein the composition comprises at least two, at least three, at least four, or at least five of  Streptococcus pneumoniae  PhtD, PhtE, PcpA, LytB and detoxified pneumolysin, or an immunogenic fragment thereof. 
     
     
         50 . The method of  claim 39  wherein the detoxified pneumolysin is a mutant pneumolysin protein comprising amino acid substitutions at positions 65, 293 and 428 of the wild type sequence. 
     
     
         51 . The method of  claim 50 , wherein the three amino acid substitutions comprise T 65 →C, G 293 →C, and C 428 →A. 
     
     
         52 . The method of  claim 39 , wherein the subject has experienced an episode of acute otitis media resulting from a  S. pneumoniae  infection and failed to achieve bacterial eradication and/or resolution of symptoms after at least 48 hours of antibiotic therapy. 
     
     
         53 . The method of  claim 39 , wherein the subject has experienced an episode of acute otitis media (AOM) resulting from a  S. pneumoniae  infection and within 14 days of completing an antibiotic treatment course for the AOM, the symptoms of AOM returned.