Protein-based streptococcus pneumoniae vaccines

Abstract

The present invention is primarily directed to a method for preventing infection of a mammalian subject with S. pneumoniae, wherein said method comprises administering to said subject an effective amount of one or more S. pneumoniae cell wall and/or cell membrane proteins and/or immunogenically-active fragments, derivatives or modifications thereof, wherein said proteins are selected from a defined group of immunogenic proteins. The present invention further provides vaccine compositions containing said cell wall and/or cell membrane proteins.

1 . A method for protecting a mammalian subject against infection from  S. pneumoniae  by administering to said subject a vaccine composition comprising an isolated protein selected from one or more  S. pneumoniae  cell wall or cell membrane proteins or immunogenically-active protein fragments, derivatives or modifications thereof which are associated with an age-dependent immune response and which are administered in an amount effective to induce an immune response to  S. pneumoniae  to thus protect said subject from infection from  S. pneumoniae.    
     
     
         2 . The method according to  claim 1  wherein the one or more proteins are effective in all age groups, including those age groups which do not produce anti- S. pneumoniae  antibodies following inoculation with polysaccharide-based vaccines. 
     
     
         3 . The method according to  claim 2 , wherein the subject is an infant under four years of age. 
     
     
         4 . The method according to  claim 2  wherein the subject is an infant under two years of age. 
     
     
         5 . The method according to  claim 2 , wherein the subject is an elderly subject. 
     
     
         6 . The method of  claim 1  wherein said  S. pneumoniae  cell wall and/or cell membrane protein is selected from the group consisting of: phosphoenolpyruvate protein phosphotransferase (Accession No. NP — 345645, SEQ ID NO:4); phosphoglucomutase/phosphomannomutase family protein (Accession No. NP — 346006, SEQ ID NO:5); trigger factor (Accession No. NP — 344923, SEQ ID NO:6); elongation factor G/tetracycline resistance protein (tetO), (Accession No. NP — 34481 1, SEQ ID NO:7); NADH oxidase (Accession No. NP — 345923, SEQ ID NO:8); Aspartyl/glutamyl-tRNA amidotransferase subunit C (Accession No. NP — 344960, SEQ ID NO:9); cell division protein FtsZ (Accession No. NP — 346105, SEQ ID NO:10); L-lactate dehydrogenase (Accession No. NP — 345686, SEQ ID NO:11); glyceraldehyde 3-phosphate dehydrogenase (GAPDH), (Accession No. NP — 346439, SEQ ID NO:12); fructose-bisphosphate aldolase (Accession No. NP — 345117, SEQ ID NO:13); UDP-glucose 4-epimerase (Accession No. NP — 346261, SEQ ID NO:14); elongation factor Tu family protein (Accession No. NP — 358192, SEQ ID NO:15); Bifunctional GMP synthase/glutamine amidotransferase protein (Accession No. NP — 345899, SEQ ID NO:16); glutamyl-tRNA synthetase (Accession No. NP — 346492, SEQ ID NO:17); glutamate dehydrogenase (Accession No. NP — 345769, SEQ ID NO:18); Elongation factor TS (Accession No. NP — 346622, SEQ ID NO:19); phosphoglycerate kinase (TIGR4) (Accession No. AAK74657, SEQ ID NO:20); 30S ribosomal protein S1 (Accession No. NP — 345350, SEQ ID NO:21); 6-phosphogluconate dehydrogenase (Accession No. NP — 357929, SEQ ID NO:22); aminopeptidase C (Accession No. NP — 344819, SEQ ID NO:23); carbomoyl-phosphate synthase (large subunit) (Accession No. NP — 345739, SEQ ID NO:24); PTS system, mannose-specific IIAB components (Accession No. NP — 344822, SEQ ID NO:25); 30S ribosomal protein S2 (Accession No. NP — 346623, SEQ ID NO:26); dihydroorotate dehydrogenase 1B (Accession No. NP — 358460, SEQ ID NO:27); aspartate carbamoyltransferase catalytic subunit (Accession No. NP — 345741, SEQ ID NO:28); elongation factor Tu (Accession No. NP — 345941, SEQ ID NO:29); Pneumococcal surface immunogenic protein A (PsipA) (Accession No. NP — 344634, SEQ ID NO:30); phosphoglycerate kinase (R6) (Accession No. NP — 358035, SEQ ID NO:31); ABC transporter substrate-binding protein (Accession No. NP — 344690, SEQ ID NO:32); endopeptidase O (Accession No. NP — 346087, SEQ ID NO:33); Pneumococcal surface immunogenic protein B (PsipB) (Accession No. NP — 358083, SEQ ID NO:34); Pneumococcal surface immunogenic protein C (PsipC) (Accession No. NP — 345081, SEQ ID NO:35). 
     
     
         7 . The method according to  claim 1 , wherein the vaccine composition includes one or more pharmaceutically acceptable adjuvants. 
     
     
         8 . The method according to  claim 1  wherein the immune response is effective against localized infection of a mucosal tissue by  S. pneumoniae.    
     
     
         9 . The method according to  claim 8 , wherein the one or more  S. pneumoniae  proteins to be administered are lectins. 
     
     
         10 . The method according to  claim 1 , wherein the immune response is effective against systemic infection with  S. pneumoniae.    
     
     
         11 . The method according to  claim 10 , wherein the one or more  S. pneumoniae  proteins to be administered are non-lectins. 
     
     
         12 . The method according to  claim 1 , wherein the  S. pneumoniae  proteins to be administered are a mixture of lectins and non-lectins. 
     
     
         13 . The method according to  claim 1 , wherein the subject is a human subject. 
     
     
         14 . The method of  claim 1  wherein the subject is protected against  S. pneumoniae  infection by administration of the vaccine composition prior to occurrence of the infection. 
     
     
         15 . A vaccine composition comprising as the active ingredient one or more isolated protein selected from  S. pneumoniae  cell wall or cell membrane proteins or immunogenically-active fragments, derivatives or modifications thereof which are associated with an age-dependent immune response, optionally together with one or more pharmaceutically acceptable adjuvants. 
     
     
         16 . The vaccine composition according to  claim 15 , wherein said  S. pneumoniae  cell wall and/or cell membrane protein is selected from the group consisting of: phosphoenolpyruvate protein phosphotransferase (Accession No. NP — 345645, SEQ ID NO:4); phosphoglucomutase/phosphomannomutase family protein (Accession No. NP — 346006, SEQ ID NO:5); trigger factor (Accession No. NP — 344923, SEQ ID NO:6); elongation factor G/tetracycline resistance protein (tetO), (Accession No. NP — 344811, SEQ ID NO:7); NADH oxidase (Accession No. NP — 345923, SEQ ID NO:8); Aspartyl/glutamyl-tRNA amidotransferase subunit C (Accession No. NP — 344960, SEQ ID NO:9); cell division protein FtsZ (Accession No. NP — 346105, SEQ ID NO:10); L-lactate dehydrogenase (Accession No. NP — 345686, SEQ ID NO:11); glyceraldehyde 3-phosphate dehydrogenase (GAPDH), (Accession No. NP — 346439, SEQ ID NO:12); fructose-bisphosphate aldolase (Accession No. NP — 345117, SEQ ID NO:13); UDP-glucose 4-epimerase (Accession No. NP — 346261, SEQ ID NO:14); elongation factor Tu family protein (Accession No. NP — 358192, SEQ ID NO:15); Bifunctional GMP synthase/glutamine amidotransferase protein (Accession No. NP — 345899, SEQ ID NO:16); glutamyl-tRNA synthetase (Accession No. NP — 346492, SEQ ID NO:17); glutamate dehydrogenase (Accession No. NP — 345769, SEQ ID NO:18); Elongation factor TS (Accession No. NP — 346622, SEQ ID NO:19); phosphoglycerate kinase (TIGR4) (Accession No. AAK74657, SEQ ID NO:20); 30S ribosomal protein S1 (Accession No. NP — 345350, SEQ ID NO:21); 6-phosphogluconate dehydrogenase (Accession No. NP — 357929, SEQ ID NO:22); aminopeptidase C (Accession No. NP — 344819, SEQ ID NO:23); carbomoyl-phosphate synthase (large subunit) (Accession No. NP — 345739, SEQ ID NO:24); PTS system, mannose-specific IIAB components (Accession No. NP — 344822, SEQ ID NO:25); 30S ribosomal protein S2 (Accession No. NP — 346623, SEQ ID NO:26); dihydroorotate dehydrogenase 1B (Accession No. NP — 358460, SEQ ID NO:27); aspartate carbamoyltransferase catalytic subunit (Accession No. NP — 345741, SEQ ID NO:28); elongation factor Tu (Accession No. NP — 345941, SEQ ID NO:29); Pneumococcal surface immunogenic protein A (PsipA) (Accession No. NP — 344634, SEQ ID NO:30); phosphoglycerate kinase (R6) (Accession No. NP — 358035, SEQ ID NO:31); ABC transporter substrate-binding protein (Accession No. NP — 344690, SEQ ID NO:32); endopeptidase O (Accession No. NP — 346087, SEQ ID NO:33); Pneumococcal surface immunogenic protein B (PsipB) (Accession No. NP — 358083, SEQ ID NO:34); Pneumococcal surface immunogenic protein C (PsipC) (Accession No. NP — 345081, SEQ ID NO:35). 
     
     
         17 . The vaccine composition according to  claim 15 , wherein the one or more  S. pneumoniae  cell wall and/or cell membrane proteins are lectins. 
     
     
         18 . The vaccine composition according to  claim 15 , wherein the one or more  S. pneumoniae  cell wall and/or cell membrane proteins are non-lectins. 
     
     
         19 . The vaccine composition according to  claim 15 , wherein the one or more  S. pneumoniae  cell wall and/or cell membrane proteins are a mixture of lectins and non-lectins. 
     
     
         20 . The vaccine composition according to  claim 15 , which is specifically formulated for an infant under four years of age, an infant under two years of age, or for an elderly subject.