A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host

Christian M. Harding, Mohamed A. Nasr, Nichollas E. Scott, Guillaume Goyette-Desjardins, Harald Nothaft, Anne E. Mayer, Sthefany M. Chavez, Jeremy P. Huynh, Rachel L. Kinsella, Christine M. Szymanski, Christina L. Stallings, Mariela Segura, Mario F. Feldman

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Chemical synthesis of conjugate vaccines, consisting of a polysaccharide linked to a protein, can be technically challenging, and in vivo bacterial conjugations (bioconjugations) have emerged as manufacturing alternatives. Bioconjugation relies upon an oligosaccharyltransferase to attach polysaccharides to proteins, but currently employed enzymes are not suitable for the generation of conjugate vaccines when the polysaccharides contain glucose at the reducing end, which is the case for ~75% of Streptococcus pneumoniae capsules. Here, we use an O-linking oligosaccharyltransferase to generate a polyvalent pneumococcal bioconjugate vaccine with polysaccharides containing glucose at their reducing end. In addition, we show that different vaccine carrier proteins can be glycosylated using this system. Pneumococcal bioconjugates are immunogenic, protective and rapidly produced within E. coli using recombinant techniques. These proof-of-principle experiments establish a platform to overcome limitations of other conjugating enzymes enabling the development of bioconjugate vaccines for many important human and animal pathogens.

Original languageEnglish
Article number891
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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