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EP-3474890-B1 - PNEUMOCOCCAL POLYSACCHARIDE-PROTEIN CONJUGATE COMPOSITION

EP3474890B1EP 3474890 B1EP3474890 B1EP 3474890B1EP-3474890-B1

Inventors

  • SEEBERGER, PETER H.
  • XU, Fei-fei
  • KHAN, Naeem
  • KAPLONEK, Paulina
  • LYKKE, Lennart
  • PEREIRA, Claney Lebev
  • EMMADI, Madhu
  • CALOW, Adam
  • PARAMESWARAPPA, Sharavathi Guddehalli
  • MENOVA, Petra
  • LISBOA, Marilda
  • MARTIN, CHRISTOPHER
  • SCHUMANN, Benjamin

Dates

Publication Date
20260506
Application Date
20170622

Claims (10)

  1. An immunogenic composition comprising a conjugate of a saccharide from Streptococcus pneumoniae serotype 8 and a carrier protein, and a mixture consisting of capsular polysaccharides from Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F individually conjugated to CRM 197 carrier protein; wherein the conjugate of a saccharide from Streptococcus pneumoniae serotype 8 and a carrier protein is of the following general formula (I): [V*-U x+3 -U x+2 -U x+1 -U x -O-L 1 -NH-W 1 ] m1 -carrier-protein1 ( I ) wherein x is 3; V*- represents H-; R # represents -CH 2 OH; L 1 represents -(CH 2 ) o -; o represents 2; m1 is comprised between 8 and 15; -W 1 - represents a1 represents 4; and carrier-protein1 represents CRM 197 .
  2. The immunogenic composition according to claim 1, further comprising a Streptococcus pneumoniae serotype 2 conjugate of the following general formula (II-C) [B*-A y+3 -A y+2 -A y+1 -A y -O-L 2 -NH-W 2 ] m2 -carrier-protein2 ( II-C ) wherein y is an integer selected from 1, 2, 3 and 4; B*- represents H-, H-A y -, H-A y+1 -A y -, H-A y+2 -A y+1 -A y - or H-A y+3 -A y+2 -A y+1 -A y -; L 2 represents a linker; m2 is comprised between about 2 and about 18; -W 2 - is selected from: a2 represents an integer from 1 to 10; b2 represents an integer from 1 to 4; and carrier-protein2 is selected from CRM 197 , protein D, tetanus toxoid and diphtheria toxoid.
  3. The immunogenic composition according to claim 2, wherein the Streptococcus pneumoniae serotype 2 conjugate has the following general formula (II) [B*-A y+3 -A y+2 -A y+1 -A y -O-L 2 -NH-W 2 ] m2 -carrier-protein2 ( II ) wherein and y, B*-, L 2 , m2, -W 2 - and carrier-protein2 have the meanings as defined in claim 3.
  4. The immunogenic composition according to claim 2, wherein the Streptococcus pneumoniae serotype 2 conjugate has the following general formula (II-D) [B*-A y+3 -A y+2 -A y+1 -A y -O-L 2 -NH-W 2 ] m2 -carrier-protein2 ( II-D ) wherein and y, B*-, L 2 , m2, -W 2 - and carrier-protein2 have the meanings as defined in claim 3.
  5. The immunogenic composition according to any one of the claims 2 - 4, wherein y represents 1 and/or B*- represents H-.
  6. The immunogenic composition according to any one of claims 1 to 5, wherein the conjugate of a saccharide from Streptococcus pneumoniae serotype 8 and a carrier protein is
  7. The immunogenic composition according to any one of the claims 1 - 6 for use in the prevention and/or treatment of diseases caused by Streptococcus pneumoniae.
  8. The immunogenic composition according to any one of the claims 2 - 7 for use in the prevention and/or treatment of diseases caused by Streptococcus pneumoniae serotype 8 and/or serotype 2.
  9. A vaccine comprising the immunogenic composition according to any one of the claims 1 - 6, a physiologically acceptable vehicle and an adjuvant.
  10. The vaccine according to claim 9, wherein the adjuvant is aluminium phosphate.

Description

Field of the invention The present invention relates to immunogenic compositions comprising a conjugate of a saccharide from Streptococcus pneumoniae serotype 8 and a carrier protein, and a mixture consisting of capsular polysaccharides from Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F individually conjugated to CRM197 carrier protein. Said compositions are useful for the prevention and/or treatment of diseases caused by Streptococcus pneumoniae, including Streptococcus pneumoniae serotype 8. Background of the invention Streptococcus pneumoniae (S. pneumoniae) commonly known as pneumococci or diplococci is a human pathogenic Gram positive bacterium encapsulated with capsular polysaccharide. Based on the chemical nature of the polysaccharide capsule, pneumococci have been classified into more than 90 serotypes. Pneumococcus is a commensal bacterium that asymptomatically colonizes in the upper respiratory tract of human and is responsible for causing pneumonia, septicemia, meningitis and otitis media. Pneumococci is the most common cause of vaccine-preventable deaths in children aged <5 years and elderly peoples worldwide. Global estimates suggest that 18% of all deaths in children less than 5 years of age occur due to pneumonia. Capsular polysaccharide is one of the major virulence factors responsible for pneumococcal pathogenesis. The spectrum of prevailing capsular types varies with age, time and geographical region, although common serotypes are consistently identified throughout the world. Globally, about 20 serotypes are associated with > 80% of invasive pneumococcal disease occurring in all age groups; the 13 most common serotypes cause at least 70-75% of invasive disease in children. Pneumococcal vaccines that are currently available are capsular polysaccharide based and designed to cover the serotypes most frequently associated with invasive pneumococcal disease. The available 23-valent polysaccharide vaccine (23-PPV) is not effective in children less than 2 years of age, while the 7-valent conjugate vaccines (7-PCV) is effective in children, but has limited serotype coverage. To increase the serotype coverage, 10-valent conjugate vaccine containing the conjugates of the capsular polysaccharides from S. pneumoniae type 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and protein D (a non-typeable Haemophilus influenzae protein), tetanus toxoid and diphtheria toxoid protein, and 13-valent conjugate vaccine containing the conjugates of capsular polysaccharides from S. pneumoniae type 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and diphtheria CRM197 protein have been licensed for use. The 13-valent conjugate vaccine provides comprehensive coverage for over 85% of epidemiologically important pneumococcal serotypes in the United States and throughout the world. In immunization experiments performed with this vaccine, both polysaccharide binding IgG and opsonophagocytic antibodies were elicited to each of the vaccine's 13 serotypes. The by far least-efficient serotype in the current pneumococcal conjugate vaccine is Streptococcus pneumoniae serotype 3 (ST3) (63.5 % responders by antipolysaccharide IgG according to Table 2 in Gruber et al., ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 2012, 1263, p. 15). The international patent application WO2016046420A1 discloses synthetic saccharides derived from S. pneumoniae serotype 8 and the corresponding conjugates with carrier proteins. Further, the immune response raised in rabbits was evaluated with a synthetic tetrasaccharide and a synthetic hexasaccharide conjugated to the carrier protein CRM197. All rabbits immunized with the conjugates showed a marked immune response against S. pneumoniae serotype 8 capsular polysaccharide. The structure of the S. pneumoniae polysaccharide of serotype 8 was described by Jones et al. in J. Am. Chem. Soc. 1957, 79, p. 2787. The authors found out by acid hydrolysis that the S. pneumoniae polysaccharide of serotype 8 is a linear having a repeating unit of -β-D-GlcAp-(1→4)-β-D-Glcp-(1→4)-α-D-Glcp-(1→4)-α-D-Galp-(1→4)-. The review Microbiological Rev. 1995, 59, p. 591 reports on S. pneumoniae virulence factors, pathogenesis and vaccines. Pneumococcal polysaccharide vaccines and pneumococcal saccharide-protein vaccines are described. Pneumococcal polysaccharide vaccines only elicit long-lasting antibodies and protection in healthy adults, while these vaccines are poorly immunogenic in children and elderly people. Pneumococcal saccharide-protein vaccines show an enhanced immunogenicity, which is assumed to be caused by the T-cell dependent antigen-character of the conjugate. Further, the immunogenicity of saccharide-protein conjugates depends on their structural characteristics, namely the saccharide length and terminal structures, the nature of the carrier protein, the ratio saccharide/protein and the coupling chemistry. Based on recent experimental results which support the fact that pr