Journal article
A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host
CM Harding, MA Nasr, NE Scott, G Goyette-Desjardins, H Nothaft, AE Mayer, SM Chavez, JP Huynh, RL Kinsella, CM Szymanski, CL Stallings, M Segura, MF Feldman
Nature Communications | NATURE PUBLISHING GROUP | Published : 2019
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 reduci..
View full abstractGrants
Awarded by Burroughs Wellcome Fund
Funding Acknowledgements
We would like to thank Brendan Wren and Laura Yates for providing the pB-8 plas-mid<SUP>49</SUP>. We would like to thank Andrew Webb from Walter Eliza Hall institute of medical research for providing mass spectrometry support for the peptide-based analysis. We would also like to thank the Melbourne Mass Spectrometry and Proteomics Facility of The Bio21 Molecular Science and Biotechnology Institute at The University of Melbourne for the support, maintenance, and access to mass spectrometry infrastructure for intact protein-based analysis. This work was funded by National Institute for Allergy and Infectious Disease (NIAID) R41 AI131742 grant awarded to M.F.F. and VaxNewMo. This work was partially supported by National Health and Medical Research Council of Australia (NHMRC) project grants awarded to N.E.S. (APP1100164). N.E.S. was supported by an Overseas (Biomedical) Fellowship (APP1037373) and a University of Melbourne Early Career Researcher Grant Scheme (Proposal number 603107). J.P.H. was supported by a National Science Foundation Graduate Research Fellowship (DGE-1143954), R.L.K. was supported by a Potts Memorial Foundation Postdoctoral Fellowship, and C.L.S. was supported by a Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award.