Vaccine comprising
The present invention relates to an immunogenic composition comprising S. pneumoniae capsular saccharide conjugates from serotypes 19A and 19F wherein 19A is conjugated to a first bacterial toxoid and 19F is conjugated to a second bacterial toxoid. Methods of making and uses thereof are also described.
1. A multivalent Streptococcus pneumoniae immunogenic composition comprising components including saccharide conjugate components, wherein the saccharide conjugate components consist of conjugates of capsular saccharides of twelve different serotypes of Streptococcus pneumoniae , wherein the different serotypes are 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, wherein the capsular saccharides of at least 4 of the twelve different serotypes of Streptococcus pneumoniae are separately conjugated to 4 different carrier proteins either directly or by a linker, wherein the capsular saccharide of the 19A and 6A serotypes are conjugated to a bacterial toxoid either directly or by a linker, and the capsular saccharide of the 19F serotype is conjugated to diphtheria toxoid either directly or by a linker, the capsular saccharide of the 18C serotype is conjugated to tetanus toxoid either directly or by a linker, and wherein the Streptococcus pneumoniae capsular saccharides from the 1, 4, 5, 6B, 7F, 9V, 14 and 23F serotypes are conjugated to protein D from Haemophilus influenzae either directly or by a linker, and wherein the serotype 18C capsular saccharide has an average saccharide size of 89-97 kDa, and wherein the immunogenic composition comprises an adjuvant, wherein the adjuvant is selected from the group consisting of a metal salt, an oil in water emulsion, a Toll like receptor agonist, a saponin, and a combination thereof.
2. The multivalent Streptococcus pneumoniae immunogenic composition of claim 1 wherein the bacterial toxoid conjugated to the capsular saccharide of the 19A serotype is different from diphtheria toxoid.
3. The multivalent Streptococcus pneumoniae immunogenic composition of claim 1 wherein the bacterial toxoid conjugated to the capsular saccharide of the 19A serotype or the 6A serotype is selected from the group consisting of tetanus toxoid, CRM197, pertussis toxoid, a bacterial cytolysin and pneumolysin.
4. The multivalent Streptococcus pneumoniae immunogenic composition of claim 1 which further comprises one or more unconjugated or conjugated S. pneumoniae proteins.
5. The multivalent Streptococcus pneumoniae immunogenic composition of claim 4 wherein said one or more S. pneumoniae proteins are selected from Polyhistidine 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.
6. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 which comprises pneumolysin as a free protein or a carrier protein.
7. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 which comprises a Polyhistidine Triad family (PhtX) protein as a free protein or a carrier protein.
8. A method of inducing an immune response in a human against Streptococcus pneumoniae comprising administering to the human an effective amount of the multivalent Streptococcus pneumoniae immunogenic composition of claim 1 .
9. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the dose of the capsular saccharide conjugate of the 19A serotype is between 1-10 μg.
10. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the dose of the capsular saccharide conjugate of the 19A serotype is between 2-8 μg.
11. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the capsular saccharide of the 19A serotype is conjugated to the bacterial toxoid directly using CDAP chemistry.
12. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 , wherein the capsular saccharide of the 18C serotype is conjugated to the tetanus toxoid via the ADH linker.
13. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the capsular saccharide of the 18C serotype is sized by microfluidisation.
14. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the adjuvant is selected from a metal salt and a Toll like receptor agonist and wherein the metal salt is an aluminum salt.
15. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 1 wherein the adjuvant is selected from an aluminum salt and a Toll like receptor agonist and the aluminum salt is an aluminum phosphate salt and the Toll like receptor is a Toll like receptor 4 agonist.
16. The multivalent Streptococcus pneumoniae immunogenic composition according to claim 15 wherein the Toll like receptor 4 agonist is 3D-MPL.