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 and Mario F. Feldman ()
Additional contact information
Christian M. Harding: VaxNewMo LLC
Mohamed A. Nasr: University of Alberta
Nichollas E. Scott: University of Melbourne at the Peter Doherty
Guillaume Goyette-Desjardins: University of Montreal
Harald Nothaft: University of Alberta
Anne E. Mayer: Washington University School of Medicine
Sthefany M. Chavez: Washington University School of Medicine
Jeremy P. Huynh: Washington University School of Medicine
Rachel L. Kinsella: Washington University School of Medicine
Christine M. Szymanski: University of Georgia
Christina L. Stallings: Washington University School of Medicine
Mariela Segura: University of Montreal
Mario F. Feldman: VaxNewMo LLC

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08869-9

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