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An efficient cell free enzyme-based total synthesis of a meningococcal vaccine candidate

Domain:

healthcare

Record type:

paper
Creator:
TimMarDavRob
Publisher:
Spr
Host:
Abstract Invasive meningococcal disease (IMD) is a global health problem and vaccination has proven the most effective way of disease control. Neisseria meningitidis serogroup X ( Nm X) is an emerging threat in the African sub-Saharan meningitis belt, but no vaccine is available today. Leading vaccines against Nm are glycoconjugates, in which capsular polysaccharides isolated from large-scale pathogen cultures are conjugated to adjuvant proteins. Though safe and efficacious even in infants, high costs and biohazard associated with the production limit abundant application of glycoconjugate vaccines particularly in the most afflicted nations. An existing Nm X vaccine candidate (CPSXn-CRM 197 ) produced by established protocols from Nm X capsule polysaccharide (CPSX) has been shown to elicit high bactericidal immunoglobulin G titres in mice. Here we describe the scalable in vitro synthesis of CPSXiv from chemically pure precursors by the use of recombinant Nm X capsule polymerase. Application of the described coupling chemistry gives CPSXiv-CRM 197 , which in mouse vaccination experiments behaves identical to the benchmark CPSXn-CRM 197 . Excluding any biohazards, this novel process represents a paradigm shift in vaccine production and a premise towards vaccine manufacturing in emerging economies.

Visit

doi.org

Licenses

https://creativecommons.org/licenses/by/4.0https://creativecommons.org/licenses/by/4.0

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