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US-12616744-B2 - Immunogenic compositions comprising conjugated capsular saccharide antigens and uses thereof

US12616744B2US 12616744 B2US12616744 B2US 12616744B2US-12616744-B2

Abstract

The present invention relates to new immunogenic compositions comprising conjugated Streptococcus pneumoniae capsular saccharide antigens (glycoconjugates) and uses thereof. Immunogenic compositions of the present invention will typically comprise at least one glycoconjugate from a S. pneumoniae serotype not found in PREVNAR®, SYNFLORIX® and/or PREVNAR 13®. The invention also relates to vaccination of human subjects, in particular infants and elderly, against pneumococcal infections using said novel immunogenic compositions.

Inventors

  • Emilio Anthony Emini
  • Michael William Pride
  • Kathrin Ute Jansen
  • Wendy Jo Watson
  • Avvari Krishna Prasad
  • Mingming Han
  • Jin-Hwan Kim
  • Jianxin Gu
  • Yu-Ying Yang
  • Rajesh Kumar Kainthan
  • David Cooper

Assignees

  • PFIZER INC.

Dates

Publication Date
20260505
Application Date
20231206

Claims (19)

  1. 1 . A 21-valent immunogenic composition comprising glycoconjugates of capsular polysaccharide from Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F and 33F individually conjugated to a carrier protein, wherein the carrier protein of the glycoconjugates respectively comprising capsular polysaccharide of serotypes 8, 10A, 11A, 12F and 33F is CRM 197 , and wherein the carrier protein of the glycoconjugates respectively comprising capsular saccharide of serotypes 15B and 22F is tetanus toxoid.
  2. 2 . The 21-valent immunogenic composition of claim 1 , wherein the carrier protein of the glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F and 23F is CRM 197 .
  3. 3 . The 21-valent immunogenic composition of claim 2 , wherein the carrier protein of the glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 7F and 9N is CRM 197 .
  4. 4 . The 21-valent immunogenic composition of claim 3 , wherein the carrier protein of the glycoconjugates respectively comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 1 and 5 is tetanus toxoid.
  5. 5 . The 21-valent immunogenic composition of claim 4 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 15B comprise at least 0.1 mM acetate per 1 mM of the respective capsular polysaccharide.
  6. 6 . The 21-valent immunogenic composition of claim 5 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 15B comprise at least 0.5 mM acetate per 1 mM of the respective capsular polysaccharide.
  7. 7 . The 21-valent immunogenic composition of claim 6 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 15B comprise less than 50% free polysaccharide.
  8. 8 . The 21-valent immunogenic composition of claim 4 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 22F comprise at least 0.1 mM acetate per 1 mM of the respective capsular polysaccharide.
  9. 9 . The 21-valent immunogenic composition of claim 8 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 22F comprise at least 0.5 mM acetate per 1 mM of the respective capsular polysaccharide.
  10. 10 . The 21-valent immunogenic composition of claim 9 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 22F comprise less than 50% free polysaccharide.
  11. 11 . The 21-valent immunogenic composition of claim 4 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 33F comprise at least 0.1 mM acetate per 1 mM of the respective capsular polysaccharide.
  12. 12 . The 21-valent immunogenic composition of claim 11 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 33F comprise at least 0.5 mM acetate per 1 mM of the respective capsular polysaccharide.
  13. 13 . The 21-valent immunogenic composition of claim 12 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 33F comprise less than 50% free polysaccharide.
  14. 14 . The 21-valent immunogenic composition of claim 4 , wherein said glycoconjugates comprising capsular polysaccharide of Streptococcus pneumoniae serotypes 15B, 22F and 33F comprise at least 0.5 mM acetate per 1 mM of the respective capsular polysaccharide and comprise less than 50% free polysaccharide of each respective capsular polysaccharide.
  15. 15 . The multivalent immunogenic composition of claim 4 , further comprising an adjuvant and a pharmaceutically acceptable excipient, carrier, or diluent.
  16. 16 . The multivalent immunogenic composition of claim 15 , wherein said multivalent immunogenic composition comprises 2.0 μg to 5.0 μg capsular saccharide of each Streptococcus pneumoniae serotype.
  17. 17 . The multivalent immunogenic composition of claim 16 , wherein said multivalent immunogenic composition comprises about 4.4 μg capsular saccharide of Streptococcus pneumoniae serotype 6B and about 2.2 μg capsular saccharide of each of the other Streptococcus pneumoniae serotypes.
  18. 18 . The multivalent immunogenic composition of claim 16 , wherein said multivalent immunogenic composition comprises 15 μg to 100 μg carrier protein.
  19. 19 . The multivalent immunogenic composition of claim 16 , wherein said multivalent immunogenic composition comprises 40 μg to 100 μg carrier protein.

Description

CROSS REFERENCE TO RELATED APPLICATION This application is a divisional application of U.S. application Ser. No. 17/194,224, filed Mar. 6, 2021, issued as U.S. Pat. No. 11,872,274, which is a divisional of U.S. application Ser. No. 16/899,738, filed Jun. 12, 2020, issued as U.S. Pat. No. 11,090,375, which is a continuation of U.S. application Ser. No. 15/286,696, filed Oct. 6, 2016, issued as U.S. Pat. No. 11,160,855, which is a divisional of U.S. application Ser. No. 14/597,488, filed Jan. 15, 2015, issued as U.S. Pat. No. 9,492,559, which claims the priority benefit of U.S. Provisional Application No. 61/929,547, filed Jan. 21, 2014, the entireties of which are hereby incorporated by reference herein. REFERENCE TO SEQUENCE LISTING This application includes an electronically submitted Sequence Listing XML file named “PC072040E Sequence Listing.xml” created on Dec. 6, 2023 and having a size of 51,967 bytes. The material in the Sequence Listing XML file “PC072040E Sequence Listing.xml” is part of the specification and is incorporated by reference herein in its entirety. FIELD OF THE INVENTION The present invention relates to new immunogenic compositions comprising conjugated capsular saccharide antigens (glycoconjugates) and uses thereof. Immunogenic compositions of the present invention will typically comprise glycoconjugates, wherein the saccharides are derived from serotypes of Streptococcus pneumoniae. The invention also relates to vaccination of human subjects, in particular infants and elderly, against pneumococcal infections using said novel immunogenic compositions. BACKGROUND OF THE INVENTION Infections caused by pneumococci are a major cause of morbidity and mortality all over the world. Pneumonia, febrile bacteraemia and meningitis are the most common manifestations of invasive pneumococcal disease, whereas bacterial spread within the respiratory tract may result in middle-ear infection, sinusitis or recurrent bronchitis. Compared with invasive disease, the non-invasive manifestations are usually less severe, but considerably more common. In Europe and the United States, pneumococcal pneumonia is the most common community-acquired bacterial pneumonia, estimated to affect approximately 100 per 100,000 adults each year. The corresponding figures for febrile bacteraemia and meningitis are 15-19 per 100000 and 1-2 per 100,000, respectively. The risk for one or more of these manifestations is much higher in infants and elderly people, as well as immune compromised persons of any age. Even in economically developed regions, invasive pneumococcal disease carries high mortality; for adults with pneumococcal pneumonia the mortality rate averages 10%-20%, whilst it may exceed 50% in the high-risk groups. Pneumonia is by far the most common cause of pneumococcal death worldwide. The etiological agent of pneumococcal diseases, Streptococcus pneumoniae (pneumococcus), is a Gram-positive encapsulated coccus, surrounded by a polysaccharide capsule. Differences in the composition of this capsule permit serological differentiation between about 91 capsular types, some of which are frequently associated with pneumococcal disease, others rarely. Invasive pneumococcal infections include pneumonia, meningitis and febrile bacteremia; among the common non-invasive manifestations are otitis media, sinusitis and bronchitis. Pneumococcal conjugate vaccines (PCVs) are pneumococcal vaccines used to protect against disease caused by S. pneumoniae (pneumococcus). There are currently three PCV vaccines available on the global market: PREVNAR® (called PREVENAR® in some countries) (heptavalent vaccine), SYNFLORIX® (a decavalent vaccine) and PREVNAR 13® (tridecavalent vaccine). The recent development of widespread microbial resistance to essential antibiotics and the increasing number of immunocompromised persons underline the need for pneumococcal vaccines with even broader protection. In particular, there is a need to address remaining unmet medical need for coverage of pneumococcal disease due to serotypes not found in PREVNAR 13® and potential for serotype replacement over time. The specific serotypes causing disease beyond the 13 in PREVNAR 13® vary by region, population, and may change overtime due to acquisition of antibiotic resistance, pneumococcal vaccine introduction and secular trends of unknown origin. There is a need for immunogenic compositions that can be used to induce an immune response against additional Streptococcus pneumoniae serotypes in humans and in particular in children less than 2 years old. An object of the new immunogenic compositions of the present invention is to provide for appropriate protection against S. pneumoniae serotypes not found in PREVNAR 13®. In one aspect, an object of the immunogenic compositions of the present invention is to provide for appropriate protection against S. pneumoniae serotypes not found in PREVNAR® (heptavalent vaccine), SYNFLORIX® and/or PREVNAR 13® while maintaining a