Glycoconjugate vaccines are very important to public health as evident by the decrease in incidence of targeted diseases and the increase in the number of such vaccines in development. While these are very effective tools for controlling and preventing infectious diseases caused by encapsulated bacteria, there are difficulties in production, control and regulation of glycoconjugate vaccine manufacture. These vaccines are often prepared by chemical conjugation of a saccharide antigen to carrier protein with only modest coupling efficiency. Glycoconjugate vaccines are prepared by random coupling methods, which results in a product whose active ingredient is not well defined and is not easily characterized in detail. We have developed alternate methodologies for preparation of glycoconjugate vaccines to address some of these problems. The efficiency of conjugation by reductive amination was improved by introducing hydrazide groups on the carrier protein. Hydrazide based reduction amination was used to prepare a vaccine against Group A meningococcal meningitis.  This vaccine, MenAfriVac, has dramatically reduced disease in the meningitis belt of Africa. The  hydrazide based reductive amination method was also applied to preparation of glycoconjugates of pneumococcal polysaccharides. Recombinant carrier proteins with known crystal structures are being employed to reduce the ambiguities in vaccine structure. A glycoconjugate vaccine against cholera was prepared based on the O-specific polysaccharide of LPS and the non-toxic Hc fragment of tetanus toxin. Recombinant Hc fragment is easily purified and has a definable structure. We used enzymes of pathways for bacterial polysaccharide biosynthesis to chemoenzymatically prepare a Group C meningococcal polysaccharide glycoconjugate. We used mass spectrometry to map the location of conjugation sites on the carrier protein. This work was partially supported by a CRADA between FDA and PATH, Seattle, WA. �My comments are an informal communication and represent my own best judgment. These comments do not bind or obligate FDA.�

Alternate technology for preparation of glycoconjugate vaccines

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.