Bioconjugation for vaccine production

Glycoconjugate vaccines, where a surface polysaccharide from a pathogen is attached to an immunogenic protein, are among the safest and most efficacious vaccines in use today, and are a major focus for novel vaccine development. The standard approach to production is a chemical conjugation process that necessitates long development timelines, as the process requires extensive optimization for each individual target antigen. Additionally, the complexity of the production process results in high costs for such products.

LimmaTech Biologics uses a proprietary in vivo enzyme-based production method that alleviates the issues associated with the chemical conjugation process. At the core of this approach is a bacterial enzyme capable of forming precise linkages between glycan and protein moieties. The versatility of this platform combined with our extensive glycoengineering experience enables the development of innovative vaccines for multiple pathogens that has not been possible previously. Development timelines are greatly reduced, meaning vaccines can be ready for clinical testing sooner. The use of a recombinant E. coli host for production eliminates the requirement for culturing vast quantities of pathogenic bacteria, making the bioconjugation process safer than standard methods. By avoiding the harsh chemical activation process required to generate a chemical conjugate, the natural conformation of the antigenic components is preserved.

Bioconjugates are produced in a one-step process, i.e. from start to finish in vivo within a genetically engineered E. coli cell. Scale up is straightforward and robust, reliably delivering the same quality of product. In contrast to chemical conjugation, only a single round of purification is required to isolate the finished bioconjugate from the host cell, greatly reducing the time and cost associated with production and downstream processing. The precision of the conjugation reaction, whereby the conjugating enzyme targets only very specific sites on the protein results in a homogeneous product confirmed by low batch-to-batch variation, and straightforward analytical requirements.

Bioconjugation is a GSK technology and LimmaTech has an exclusive research and development agreement to develop it. The vaccine candidates against Klebsiella and Shigella were produced using this technology.