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Fast and Efficient Method for Chemoenzymatic Production of Neisseria meningitidis Glycoconjugate Vaccines

Reference Number TO 15-00377

Challenge

Infection with Neisseria meningitidis (Nm) is the cause for meningitis and other forms of meningococcal disease such as severe sepsis development. Six of all 12 known serogroups are responsible for almost all acute illnesses, with serogroups A and X being most prevalent in the African meningitis belt. While successful vaccine campaigns for serotype A have been established over the last years, no vaccination against serotype X is available today. Moreover, distribution of most effective glycoconjugate vaccines is limited due to high production cost caused by the need of cultivation of pathogens and subsequent isolation of capsular polysaccharides. Therefore, an in vitro method for producing Neisseria meningitidis capsular polysaccharides could lower production cost and speed up development of novel vaccines urgently needed.

Oldrini et al. ACS Chem. Biol. 2018, 13, 984−994
Oldrini et al. ACS Chem. Biol. 2018, 13, 984−994

Technology

The present invention provides a method for the tailored synthesis of Nm capsular oligosaccharides of defined length. By specific truncation, optimized recombinant versions of capsular polymerases from Nm serotypes A and X have been generated. Solid-phase coupling of engineered enzymes further enables rapid production of oligosaccharides with high yield and purity. Product-length control is achieved by adjusting the donor to acceptor ratio of applied sugars. Thus, the present invention allows efficient, economical and fast in vitro production of Nm capsule oligosaccharides, which are ready for activation and coupling for glycoconjugate vaccine production.

Commercial Opportunity

In-licensing or collaboration for further development is possible.

Developmental Status

Protocols for efficient synthesis of CPSA and CPSX of avDP15 (average degree of polymerization) using standard laboratory equipment have been established.

Patent Situation

European (EP3131576) and US (US2017/037440) patent applications with priority of 2014 are pending.

Further Reading

Fiebig et al. (2018) Efficient solid-phase synthesis of meningococcal capsular oligosaccharides enables simple and fast chemoenzymatic vaccine production. J Biol Chem. 2018 Jan 19;293(3):953-962.

Oldrini et al. (2018) Combined Chemical Synthesis and Tailored Enzymatic Elongation Provide Fully Synthetic and Conjugation-Ready Neisseria meningitidis Serogroup X Vaccine Antigens. ACS Chem. Biol., 2018, 13 (4), pp 984–994.