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

Nature Communications
Christian M HardingMario F Feldman

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.

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Citations

Apr 17, 2019·Glycobiology·Christian M Harding, Mario F Feldman
Aug 29, 2019·Proceedings of the National Academy of Sciences of the United States of America·Mario F FeldmanChristian M Harding
Oct 9, 2019·International Journal of Molecular Sciences·Fiona F HagerChristina Schäffer
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Jul 19, 2020·Annual Review of Microbiology·Chris WhitfieldCaitlin Sande
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Nov 3, 2021·ACS Chemical Biology·Harald NothaftChristine M Szymanski
Dec 7, 2021·Frontiers in Microbiology·Harald NothaftChristine M Szymanski

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Datasets Mentioned

BETA
ENV58402

Methods Mentioned

BETA
glycosylation
glycosylating
glycosylate
enzyme-linked immunosorbent assay
ELISAs
glycosylates
ELISA
electrophoresis
Infrared Imaging
PCR

Software Mentioned

Expasy FindPept
MassHunter

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