Bioconjugation, an elegantly simple solution to improve conjugate vaccines  

Polysaccharide conjugate (glycoconjugate) vaccines have been enormously successful at reducing disease and deaths due to infections caused by the bacterial pathogens Haemophilus influenzae type B, Streptococcus pneumoniae, Neisseria meningitidis, and Salmonella typhi. These vaccines also fight antimicrobial resistance by reducing the use of antibiotics.

Conventional conjugate vaccine manufacturing methods are complex and require chemical cross-linking of the bacterial polysaccharide antigens to immunogenic carrier proteins. The resulting vaccines are very difficult to make reproducibly and to characterize, requiring many release tests before they can be used. The non-specific cross-linking and the conditions required for chemical conjugation can also lead to undesired modifications of epitopes that could impact the quality of the immune response to the polysaccharide antigen.

Bioconjugation offers an elegantly simple alternative to chemical conjugation. Our company Co-Founder Mario Feldman is a pioneer in the field of bioconjugation, and his work has led to the industrialization of bioconjugate vaccine technologies by GSK (after acquiring GlycoVaxyn/Limmatech’s bioconjugate platform technology) for vaccine candidates against Shigella (Phase 1/2) and Klebsiella pneumoniae (Phase 1).  Janssen licensed the same platform to develop a bioconjugate vaccine against extraintestinal pathogenic Escherichia coli (ExPEC) targeting 9 serotypes (Phase 3). The use of bioconjugate vaccines has therefore been validated and de-risked by these multiple clinical-stage candidates from leading vaccine companies.

The Omniose bioconjugate platform greatly expands the range of potential bacterial targets

Three components are required for producing polysaccharide conjugate vaccines via bioconjugation – (1) a gene cluster encoding for the machinery to produce a polysaccharide antigen, (2) an engineered carrier protein to be glycosylated, and (3) a conjugating enzyme that precisely attaches the polysaccharide antigen to the carrier protein.  Because bioconjugation is enzymatically driven, surface polysaccharide epitopes are completely preserved as the native polysaccharide is attached to the carrier protein in an unmodified, natural conformation. This added feature of bioconjugation ensures that each building block of the polysaccharide retains critical epitopes important for immunogenicity and eliciting protective, functional antibody responses.

While other bioconjugation technologies have been employed to produce polysaccharide conjugate vaccines, Omniose’s bioconjugation platform is the most versatile described to date. Omniose’s conjugating enzyme PgIS has the broadest polysaccharide substrate versatility of all known conjugating enzymes, transferring virtually any polysaccharide to engineered carrier proteins. Since our bioconjugate vaccines are produced in E. coli, the company can leverage well-established E. coli production technologies.

For more information on the scientific principles of Omniose’s bioconjugation platform and vaccines under development, please see our numerous peer-reviewed publications found in multiple distinguished journals. They can be viewed here.