Multivalent pneumococcal vaccine compositions comprising polysaccharide-protein conjugates

Inventors

Matur, Ramesh Venkat • Sriraman, Rajan • Chakka, Deviprasanna • Sureddi, Satyam Naidu • Burki, Rajendar • Ganti, Sreenivasa Rao • Mantena, Narender Dev • Datla, Mahima

Assignees

Biological E Ltd

Abstract

The present disclosure relates to multivalent pneumococcal vaccine compositions comprising capsular pneumococcal polysaccharide serotypes each individually conjugated to carrier proteins. When conjugated, the combination of the capsular pneumococcal polysaccharide serotype and the carrier protein is referred to herein as a polysaccharide-protein conjugate. The pneumococcal vaccine compositions may further comprise one or more of the following; a pharmaceutically acceptable carrier, a pharmaceutically acceptable diluent, a buffer, a preservative, a stabilizer, an adjuvant, and/or a lyophilization excipient. Methods of making and administering the pneumococcal vaccine compositions described herein are also provided.

Core Innovation

The invention relates to a multivalent pneumococcal vaccine composition comprising carrier proteins consisting of pneumococcal surface adhesion protein A (PsaA) and CRM197, and capsular pneumococcal polysaccharides of two or more serotypes. Each capsular pneumococcal polysaccharide is individually conjugated to a carrier protein selected from PsaA and CRM197, with at least one capsular pneumococcal polysaccharide conjugated to PsaA and at least one capsular pneumococcal polysaccharide conjugated to CRM197, and with at least one serotype of the PsaA-conjugated polysaccharide being different from a serotype of the CRM197-conjugated polysaccharide.

The PsaA used in the composition lacks the wild-type hydrophobic N-terminal leader peptide. The disclosure encompasses native versus fragmented capsular polysaccharides, and conjugation is described as polysaccharide activation and coupling to the carrier proteins via spacers/linkers.

The resulting conjugate vaccine compositions can provide immune-response advantages over unconjugated pneumococcal polysaccharides, including improved IgG titers for selected serotypes when conjugated to PsaA in comparative immunogenicity experiments. Characterization and formulation aspects are described, including analytical methods such as SEC-HPLC and SEC-MALLS and formulation components including diluents, buffers, stabilizers, adjuvants, and aluminum phosphate.

Claims Coverage

The provided claims set includes one independent claim defining the core multivalent pneumococcal vaccine composition with two carrier proteins, individually conjugated serotype-specific capsular polysaccharides, different serotypes assigned to different carriers, and PsaA lacking the wild-type hydrophobic N-terminal leader peptide. The dependent claims further refine formulation composition and dosing constraints, and narrow use to invasive pneumococcal disease (IPD).

Coverage centers on a multivalent pneumococcal vaccine composition that uses PsaA and CRM197 as carrier proteins and individually conjugates each serotype-specific capsular pneumococcal polysaccharide to either PsaA or CRM197, with different serotypes assigned to different carrier proteins, and with PsaA lacking the wild-type hydrophobic N-terminal leader peptide. Dependent claims add protein/PS and dosage-unit microgram constraints, pharmaceutically acceptable formulation components, serotype set limitations, and a use related to IPD mediated by Streptococcus pneumoniae.

Stated Advantages

Documented Applications