Vaccine

Abstract

The present invention is in the field of pneumococcal capsular saccharide conjugate vaccines. Specifically, an immunogenic composition for infants is provided comprising a multivalent Streptococcus pneumoniae vaccine comprising 2 or more capsular saccharide conjugates from different serotypes, wherein the composition comprises a serotype 22F saccharide conjugate. Such a vaccine may be used in infant populations to reduce the incidence of elderly pneumococcal disease such as exacerbations of COPD and/or IPD.

1 . An immunogenic composition for infants comprising a multivalent  Streptococcus pneumoniae  vaccine comprising 2 or more (e.g. 7, 8, 9, 10, 11, 12, 13, 14, 15) capsular saccharide conjugates from different serotypes, wherein the composition comprises a serotype 22F saccharide conjugate. 
     
     
         2 . The immunogenic composition of  claim 1  comprising  S. pneumoniae  capsular saccharide conjugates from serotypes 19A and/or 19F. 
     
     
         3 . The immunogenic composition of  claim 1  or  2 , comprising  S. pneumoniae  capsular saccharide conjugates from serotypes 19A and 19F wherein 19A is conjugated to a carrier protein which is a first bacterial toxoid and 19F is conjugated to a second bacterial toxoid. 
     
     
         4 . The immunogenic composition of  claim 3  wherein the first bacterial toxoid is a different protein to the second bacterial toxin. 
     
     
         5 . The immunogenic composition of  claim 3  or  4  wherein the first bacterial toxoid is selected from the group consisting of tetanus toxoid, diphtheria toxoid, CRM197, pertussis toxoid, a bacterial cytolysin and pneumolysin. 
     
     
         6 . The immunogenic composition of any one of  claims 3 - 5  wherein the second bacterial toxoid is selected from the group consisting of tetanus toxoid, diphtheria toxoid, CRM197, pertussis toxoid, a bacterial cytolysin and pneumolysin. 
     
     
         7 . The immunogenic composition of any one of  claims 3 - 6  wherein the first bacterial toxoid is pneumolysin. 
     
     
         8 . The immunogenic composition of any one of  claim 3 - 7  wherein the second bacterial toxoid is diphtheria toxoid. 
     
     
         9 . The immunogenic composition of any one of  claims 1 - 8  further comprising conjugates of  S. pneumoniae  capsular saccharides 4, 6B, 9V, 14, 18C and 23F. 
     
     
         10 . The immunogenic composition of  claims 1 - 9  further comprising conjugates of  S. pneumoniae  capsular saccharides 1, 5 and 7F. 
     
     
         11 . The immunogenic composition of  claims 1 - 10  further comprising a  S. pneumoniae  capsular saccharide 3 conjugate. 
     
     
         12 . The immunogenic composition of  claims 1 - 11  further comprising a  S. pneumoniae  capsular saccharide 6A conjugate. 
     
     
         13 . The immunogenic composition of any one of  claims 1 - 12  wherein 2 different carrier proteins are separately conjugated to at least 2 different  S. pneumoniae  capsular saccharide serotypes. 
     
     
         14 . The immunogenic composition of any one of  claims 1 - 12  wherein 3 different carrier proteins are separately conjugated to at least 3 different  S. pneumoniae  capsular saccharide serotypes. 
     
     
         15 . The immunogenic composition of any one of  claims 1 - 12  wherein 4 different carrier proteins are separately conjugated to at least 4 different  S. pneumoniae  capsular saccharide serotypes. 
     
     
         16 . The immunogenic composition of any one of  claims 1 - 12  wherein 5 or more different carrier proteins are separately conjugated to at least 5 different  S. pneumoniae  capsular saccharide serotypes. 
     
     
         17 . The immunogenic composition of  claims 13 - 16  comprising 2 or more of the carrier proteins selected from the following list: tetanus toxoid, diphtheria toxoid, pneumolysin, Protein D and PhtD or fusion proteins thereof. 
     
     
         18 . The immunogenic composition of  claims 1 - 17  comprising  S. pneumoniae  capsular saccharide 1 conjugated to protein D. 
     
     
         19 . The immunogenic composition of  claims 1 - 18  comprising  S. pneumoniae  capsular saccharide 3 conjugated to protein D, pneumolysin or PhtD or fusion protein thereof. 
     
     
         20 . The immunogenic composition of  claims 1 - 19  comprising  S. pneumoniae  capsular saccharide 4 conjugated to protein D. 
     
     
         21 . The immunogenic composition of  claims 1 - 20  comprising  S. pneumoniae  capsular saccharide 5 conjugated to protein D. 
     
     
         22 . The immunogenic composition of  claims 1 - 21  comprising  S. pneumoniae  capsular saccharide 6B conjugated to protein D. 
     
     
         23 . The immunogenic composition of  claims 1 - 22  comprising  S. pneumoniae  capsular saccharide 7F conjugated to protein D. 
     
     
         24 . The immunogenic composition of  claims 1 - 23  comprising  S. pneumoniae  capsular saccharide 9V conjugated to protein D. 
     
     
         25 . The immunogenic composition of  claims 1 - 24  further comprising  S. pneumoniae  capsular saccharide 14 conjugated to protein D. 
     
     
         26 . The immunogenic composition of  claims 1 - 25  comprising  S. pneumoniae  capsular saccharide 23F conjugated to protein D. 
     
     
         27 . The immunogenic composition of  claims 1 - 26  comprising  S. pneumoniae  capsular saccharide 18C conjugated to tetanus toxoid. 
     
     
         28 . The immunogenic composition of  claims 1 - 27  comprising  S. pneumoniae  capsular saccharide 19A conjugated to pneumolysin. 
     
     
         29 . The immunogenic composition of  claims 1 - 28  comprising  S. pneumoniae  capsular saccharide 22F conjugated to PhtD or fusion protein thereof. 
     
     
         30 . The immunogenic composition of  claims 1 - 29  comprising  S. pneumoniae  capsular saccharide 6A conjugated to pneumolysin or a  H. influenzae  protein, optionally protein D or PhtD or fusion protein thereof. 
     
     
         31 . The immunogenic composition according to any preceding claim comprising a 19A capsular saccharide directly conjugated to the carrier protein. 
     
     
         32 . The immunogenic composition of any one of  claims 1 - 30  wherein 19A capsular saccharide is conjugated to the carrier protein via a linker. 
     
     
         33 . The immunogenic composition of  claim 32  wherein the linker is ADH. 
     
     
         34 . The immunogenic composition of  claim 32  or  33  wherein the linker is attached to the carrier protein by carbodiimide chemistry, preferably using EDAC. 
     
     
         35 . The immunogenic composition of any one of  claims 31 - 34  wherein the 19A saccharide is conjugated to the carrier protein or to the linker using CDAP chemistry. 
     
     
         36 . The immunogenic composition of any one of  claims 1 - 35  comprising a serotype 19A conjugate where the ratio of carrier protein to 19A saccharide is between 5:1 and 1:5, 4:1 and 1:1 or 3.5:1 and 2.5:1 (w/w). 
     
     
         37 . The immunogenic composition according to any preceding claim comprising a 19F capsular saccharide directly conjugated to the carrier protein. 
     
     
         38 . The immunogenic composition of any one of  claims 1 - 36  wherein 19F capsular saccharide is conjugated to the carrier protein via a linker. 
     
     
         39 . The immunogenic composition of  claim 38  wherein the linker is ADH. 
     
     
         40 . The immunogenic composition of  claim 38  or  39  wherein the linker is attached to the carrier protein by carbodiimide chemistry, preferably using EDAC. 
     
     
         41 . The immunogenic composition of any one of  claims 37 - 40  wherein the 19F saccharide is conjugated to the carrier protein or to the linker using CDAP chemistry. 
     
     
         42 . The immunogenic composition of any one of  claims 1 - 41  comprising a 19F saccharide conjugate, wherein the ratio of carrier protein to 19F saccharide is between 5:1 and 1:5, 4:1 and 1:1 or 2:1 and 1:1 (w/w), or 1.5:1 and 1.4:1. 
     
     
         43 . The immunogenic composition according to any preceding claim comprising a 22F capsular saccharide directly conjugated to the carrier protein. 
     
     
         44 . The immunogenic composition of any one of  claims 1 - 42  comprising 22F capsular saccharide conjugated to the carrier protein via a linker. 
     
     
         45 . The immunogenic composition of  claim 44  wherein the linker is ADH. 
     
     
         46 . The immunogenic composition of  claim 44  or  45  wherein the linker is attached to the carrier protein by carbodiimide chemistry, preferably using EDAC. 
     
     
         47 . The immunogenic composition of any one of  claims 43 - 46  wherein the 22F saccharide is conjugated to the carrier protein or to the linker using CDAP chemistry. 
     
     
         48 . The immunogenic composition of any one of  claims 1 - 47  comprising a 22F saccharide conjugate, wherein the ratio of carrier protein to 22F saccharide is between 5:1 and 1:5, 4:1 and 1:1 or 2:1 and 1:1 (w/w). 
     
     
         49 . The immunogenic composition of any preceding claim comprising a 19A saccharide conjugate, wherein the average size (e.g. M w ) of the 19A saccharide is above 100 kDa 
     
     
         50 . The immunogenic composition of  claim 49  wherein the average size (e.g. M w ) of the 19A saccharide is between 50 and 800 kDa, 110 and 700 kDa, 110-300, 120-200, 130-180, or 140-160 kDa. 
     
     
         51 . The immunogenic composition of  claim 49  or  50  wherein the 19A saccharide is either a native polysaccharide or is sized by a factor of no more than ×5. 
     
     
         52 . The immunogenic composition of  claims 49 - 51  wherein the 19A saccharide has been sized by microfluidization. 
     
     
         53 . The immunogenic composition of any preceding claim comprising a serotype 19A saccharide conjugate, wherein the dose of the 19A saccharide conjugate is between 1 and 10 μg, 1 and 5 μg, or 1 and 3 μg of saccharide. 
     
     
         54 . The immunogenic composition of  claim 53  wherein the dose of the 19A saccharide conjugate is 3 μg of saccharide. 
     
     
         55 . The immunogenic composition of any preceding claim comprising a 22F saccharide conjugate, wherein the average size (e.g. M w ) of the 22F saccharide is above 100 kDa 
     
     
         56 . The immunogenic composition of  claim 55  wherein the average size (e.g. M w ) of the 22F saccharide is between 50 and 800 kDa, 110 and 700 kDa, 110-300, 120-200, 130-180, or 150-170 kDa. 
     
     
         57 . The immunogenic composition of  claim 55  or  56  wherein the 22F saccharide is either a native polysaccharide or is sized by a factor of no more than ×5. 
     
     
         58 . The immunogenic composition of  claims 55 - 57  wherein the 22F saccharide has been sized by microfluidization. 
     
     
         59 . The immunogenic composition of any preceding claim comprising a serotype 22F saccharide conjugate, wherein the dose of the 22F saccharide conjugate is between 1 and 10 μg, 1 and 5 μg, or 1 and 3 μg of saccharide. 
     
     
         60 . The immunogenic composition of  claim 59  wherein the dose of the 22F saccharide conjugate is 3 μg of saccharide. 
     
     
         61 . The immunogenic composition of any preceding claim wherein the average size (e.g. M w ) of the saccharides is above 50 kDa, e.g, 50-1600, 80-1400, 100-1000, 150-500, or 200-400 kDa. 
     
     
         62 . The immunogenic composition according to  claim 61  which comprises serotype 1 (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 100-1000, 200-800, 250-600, or 300 and 400 kDa. 
     
     
         63 . The immunogenic composition according to  claim 61  or  62  which comprises serotype 4 (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 50-500, 60-300, 70-200, or 75 and 125 kDa. 
     
     
         64 . The immunogenic composition according to  claims 61 - 63  which comprises serotype 5 (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 100-1000, 200-700, 300-500, or 350 and 450 kDa. 
     
     
         65 . The immunogenic composition according to any of  claims 61  to  64  which comprises serotype 6B (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 500-1600, 750-1500, or 1000 and 1400 kDa. 
     
     
         66 . The immunogenic composition according to any of  claims 61  to  65  which comprises serotype 7F (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 50-1000, 100-750, 150-500, or 200 and 300 kDa. 
     
     
         67 . The immunogenic composition according to any of  claims 61  to  66  which comprises serotype 9V (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 50-1000, 100-750, 150-500, 200-400, or 250 and 300 kDa. 
     
     
         68 . The immunogenic composition according to any of  claims 61  to  67  which comprises serotype 14 (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 50-1000, 100-750, 150-500, or 200 and 250 kDa. 
     
     
         69 . The immunogenic composition according to any of  claims 61  to  68  which comprises serotype 23F (saccharide conjugate) having an average saccharide size (e.g. M w ) of between 500-1500, 700-1300, 800-1100, or 900 and 1000 kDa. 
     
     
         70 . The immunogenic composition of any preceding claim which comprises serotypes 5, 6B and 23F (and optionally 6A) as native saccharides. 
     
     
         71 . The immunogenic composition of any preceding claim wherein the dose of the capsular saccharide conjugates is between 1 and 10 μg, 1 and 5 μg, or 1 and 3 μg of saccharide per conjugate. 
     
     
         72 . The immunogenic composition of any preceding claim which comprises conjugates of serotypes 4, 18C, 19F and 22F (and optionally 19A) at dosages of 3 μg of saccharide per conjugate. 
     
     
         73 . The immunogenic composition of any preceding claim which comprises conjugates of serotypes 1, 5, 6B, 7F, 9V, 14 and 23F (and optionally 6A and/or 3) at dosages of 1 μg of saccharide per conjugate. 
     
     
         74 . The immunogenic composition of any preceding claim which further comprises unconjugated  S. pneumoniae  saccharides of serotypes different from those conjugated, such that the number of conjugated and unconjugated saccharide serotypes is less than or equal to 23. 
     
     
         75 . The immunogenic composition of any preceding claim which further comprises one or more unconjugated or conjugated  S. pneumoniae  proteins. 
     
     
         76 . The immunogenic composition of  claim 75  which comprises one or more unconjugated  S. pneumoniae  proteins. 
     
     
         77 . The immunogenic composition of  claim 75  or  76  wherein said one or more  S. pneumoniae  proteins are selected from Poly Histidine Triad family (PhtX), Choline Binding Protein family (CbpX), CbpX truncates, Lytx family, LytX truncates, CbpX truncate-LytX truncate chimeric proteins, detoxified pneumolysin (Ply), PspA, PsaA, Sp128, Sp101, Sp130, Sp125 and Sp133. 
     
     
         78 . The immunogenic composition of  claims 75 - 77  which comprises pneumolysin. 
     
     
         79 . The immunogenic composition of any of  claims 75 - 78  which comprises a PhtX protein. 
     
     
         80 . The immunogenic composition according to any preceding claim which comprises pneumolysin as free or carrier protein. 
     
     
         81 . The immunogenic composition according to any preceding claim which comprises a PhtX protein as free or carrier protein. 
     
     
         82 . The immunogenic composition of  claim 81  wherein said PhtX protein is PhtD or a PhtBD or PhtDE fusion protein. 
     
     
         83 . The immunogenic composition according to any preceding claim which further comprises an adjuvant. 
     
     
         84 . The immunogenic composition of  claim 83 , wherein the adjuvant comprises a liposome carrier. 
     
     
         85 . The immunogenic composition of  claim 84 , wherein the adjuvant comprises (per 0.5 mL dose) 0.1-10 mg, 0.2-7, 0.3-5, 0.4-2, or 0.5-1 mg (e.g. 0.4-0.6, 0.9-1.1, 0.5 or 1 mg) phospholipid (for instance DOPC). 
     
     
         86 . The immunogenic composition of  claim 84  or  85 , wherein the adjuvant comprises (per 0.5 mL dose) 0.025-2.5, 0.05-1.5, 0.075-0.75, 0.1-0.3, or 0.125-0.25 mg (e.g. 0.2-0.3, 0.1-0.15, 0.25 or 0.125 mg) sterol (for instance cholesterol). 
     
     
         87 . The immunogenic composition of  claims 84 - 86 , wherein the adjuvant comprises (per 0.5 mL dose) 5-60, 10-50, or 20-30 μg (e.g. 5-15, 40-50, 10, 20, 30, 40 or 50 μg) lipid A derivative (for instance 3D-MPL). 
     
     
         88 . The immunogenic composition of  claims 84 - 87 , wherein the adjuvant comprises (per 0.5 mL dose) 5-60, 10-50, or 20-30 μg (e.g. 5-15, 40-50, 10, 20, 30, 40 or 50 μg) saponin (for instance QS21). 
     
     
         89 . The immunogenic composition of  claim 83 , wherein the adjuvant comprises an oil in water emulsion. 
     
     
         90 . The immunogenic composition of  claim 89 , wherein the adjuvant comprises (per 0.5 mL dose) 0.5-15, 1-13, 2-11, 4-8, or 5-6 mg (e.g. 2-3, 5-6, or 10-11 mg) metabolisable oil (such as squalene). 
     
     
         91 . The immunogenic composition of  claim 89  or  90 , wherein the adjuvant comprises (per 0.5 mL dose) 0.1-10, 0.3-8, 0.6-6, 0.9-5, 1-4, or 2-3 mg (e.g. 0.9-1.1, 2-3 or 4-5 mg) emulsifier (such as Tween 80). 
     
     
         92 . The immunogenic composition of  claims 89 - 91 , wherein the adjuvant comprises (per 0.5 mL dose) 0.5-20, 1-15, 2-12, 4-10, 5-7 mg (e.g. 11-13, 5-6, or 2-3 mg) tocol (such as alpha tocopherol). 
     
     
         93 . The immunogenic composition of  claims 89 - 92 , wherein the adjuvant comprises (per 0.5 mL dose) 5-60, 10-50, or 20-30 μg (e.g. 5-15, 40-50, 10, 20, 30, 40 or 50 μg) lipid A derivative (for instance 3D-MPL). 
     
     
         94 . The immunogenic composition of  claims 89 - 93 , wherein the adjuvant comprises (per 0.5 mL dose) 0.025-2.5, 0.05-1.5, 0.075-0.75, 0.1-0.3, or 0.125-0.25 mg (e.g. 0.2-0.3, 0.1-0.15, 0.25 or 0.125 mg) sterol (for instance cholesterol). 
     
     
         95 . The immunogenic composition of  claims 89 - 94 , wherein the adjuvant comprises (per 0.5 mL dose) 5-60, 10-50, or 20-30 μg (e.g. 5-15, 40-50, 10, 20, 30, 40 or 50 μg) saponin (for instance QS21). 
     
     
         96 . The immunogenic composition of  claim 83 , wherein the adjuvant comprises a metal salt and lipid A derivative. 
     
     
         97 . The immunogenic composition of  claim 96 , wherein the adjuvant comprises (per 0.5 mL dose) 100-750, 200-500, or 300-400 μg Al as aluminium phosphate. 
     
     
         98 . The immunogenic composition of  claim 96  or  97 , wherein the adjuvant comprises (per 0.5 mL dose) 5-60, 10-50, or 20-30 μg (e.g. 5-15, 40-50, 10, 20, 30, 40 or 50 μg) lipid A derivative (for instance 3D-MPL). 
     
     
         99 . A vaccine kit comprising an immunogenic composition according to any of  claims 1  to  82  and further comprising for concomitant or sequential administration an adjuvant as defined in any of  claims 83  to  98 . 
     
     
         100 . A vaccine comprising the immunogenic composition of any one of  claims 1  to  98  and a pharmaceutically acceptable excipient. 
     
     
         101 . A process for making the vaccine according to  claim 100  which comprises the step of mixing the immunogenic composition of any of  claims 1  to  98  with a pharmaceutically acceptable excipient. 
     
     
         102 . A method of immunising a human host against disease caused by  Streptococcus pneumoniae  infection comprising administering to the host an immunoprotective dose of the immunogenic composition of any one of  claims 1  to  98  or the vaccine of  claim 100 . 
     
     
         103 . The method of  claim 102 , wherein the human host is elderly, and the disease is either or both of pneumonia or invasive pneumococcal disease (IPD). 
     
     
         104 . The method of  claim 102  or  103 , wherein the human host is elderly, and the disease is exacerbations of chronic obstructive pulmonary disease (COPD). 
     
     
         105 . The method of  claim 102 , wherein the human host is infant, and the disease is otitis media. 
     
     
         106 . The method of  claim 102  or  105 , wherein the human host is infant, and the disease is meningitis and/or bacteraemia. 
     
     
         107 . The method of  claims 102 ,  105  or  106 , wherein the human host is infant, and the disease is pneumonia and/or conjunctivitis. 
     
     
         108 . The immunogenic composition of  claims 1 - 98  or the vaccine of  claim 100  for use in the treatment or prevention of disease caused by  Streptococcus pneumoniae  infection. 
     
     
         109 . A use of the immunogenic composition or vaccine of  claims 1  to  98  or vaccine of  claim 100  in the manufacture of a medicament for the treatment or prevention of diseases caused by  Streptococcus pneumoniae  infection. 
     
     
         110 . The use of  claim 109 , wherein the disease is either or both of pneumonia or invasive pneumococcal disease (IPD) of elderly humans. 
     
     
         111 . The use of  claim 109  or  110 , wherein the disease is exacerbations of chronic obstructive pulmonary disease (COPD) of elderly humans. 
     
     
         112 . The use of  claim 109 , wherein the disease is otitis media of infant humans. 
     
     
         113 . The use of  claim 109  or  112 , wherein the disease is meningitis and/or bacteraemia of infant humans. 
     
     
         114 . The use of  claims 109 ,  112  or  113 , wherein the disease is pneumonia and/or conjunctivitis of infant humans. 
     
     
         115 . A method of eliciting a protective immune response in infants against Otitis media comprising the administration as separate or combined components, sequentially or concomitantly (i) an immunogenic composition or vaccine according to any of  claims 1  to  98  and (ii) Protein D from  Haemophilus influenzae  which protein D may be free and/or conjugated. 
     
     
         116 . A method of eliciting a protective immune response to infants against  S. pneumonia  by administering the immunogenic composition or vaccine of any preceding claim. 
     
     
         117 . A method of eliciting a protective immune response to the elderly against  S. pneumonia  by administering in combination, sequentially or concomitantly (i) the immunogenic composition or vaccine of any preceding claim (ii) one or more  S. pneumoniae  surface proteins selected from the group consisting of the PhtX family and pneumolysin. 
     
     
         118 . The immunogenic composition of  claims 1 - 98  or vaccine of  claim 100 , which comprises saccharide conjugates derived from at least all the following serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F wherein the GMC antibody titre induced against one or more of the vaccine components 4, 6B, 9V, 14, 18C, 19F and 23F is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         119 . The immunogenic composition of  claim 118 , wherein the GMC antibody titre induced against serotype 4 is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         120 . The immunogenic composition of  claim 118  or  119 , wherein the GMC antibody titre induced against serotype 6B is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         121 . The immunogenic composition of  claims 118 - 120 , wherein the GMC antibody titre induced against serotype 9V is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         122 . The immunogenic composition of  claims 118 - 121 , wherein the GMC antibody titre induced against serotype 14 is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         123 . The immunogenic composition of  claims 118 - 122 , wherein the GMC antibody titre induced against serotype 18C is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         124 . The immunogenic composition of  claims 118 - 123 , wherein the GMC antibody titre induced against serotype 19F is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         125 . The immunogenic composition of  claims 118 - 124 , wherein the GMC antibody titre induced against serotype 23F is not significantly inferior to that induced by the Prevnar® vaccine in human vaccines. 
     
     
         126 . The immunogenic composition of  claims 118 - 125  which comprises a serotype 3 saccharide conjugate. 
     
     
         127 . The immunogenic composition of  claims 118 - 126  which comprises a serotype 6A saccharide conjugate. 
     
     
         128 . The immunogenic composition of  claims 118 - 127  which comprises a serotype 19A saccharide conjugate. 
     
     
         129 . The immunogenic composition of  claims 118 - 128  which comprises a serotype 22F saccharide conjugate. 
     
     
         130 . An immunogenic composition comprising at least four  S. pneumoniae  capsular saccharide conjugates containing saccharides from different  S. pneumoniae  serotypes wherein at least one saccharide is conjugated to PhtD or fusion protein thereof and the immunogenic composition is capable of eliciting an effective immune response against PhtD 
     
     
         131 . A method of preventing an elderly human host from having a pneumococcal disease caused by  Streptococcus pneumoniae  serotype 22F infection (or reducing its severity) comprising administering to an infant host (or an infant population) an immunoprotective dose of the immunogenic composition of any one of  claims 1  to  98  or the vaccine of  claim 100 . 
     
     
         132 . The method of  claim 131 , wherein the disease is either or both of pneumonia or invasive pneumococcal disease (IPD). 
     
     
         133 . The method of  claim 131  or  132 , wherein the disease is exacerbations of chronic obstructive pulmonary disease (COPD). 
     
     
         134 . A use of the immunogenic composition or vaccine of  claims 1  to  98  or vaccine of  claim 100  in the manufacture of a medicament for the prevention or reduction in severity of a disease caused by serotype 22F  Streptococcus pneumoniae  infection in elderly patients, wherein an immunoprotective dose of said composition or vaccine is administered to an infant (or infant population). 
     
     
         135 . The use of  claim 134 , wherein the disease is either or both of pneumonia or invasive pneumococcal disease (IPD) of elderly humans. 
     
     
         136 . The use of  claim 134  or  135 , wherein the disease is exacerbations of chronic obstructive pulmonary disease (COPD) of elderly humans.