A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Nature communications - 10(2019), 1 vom: 21. Feb., Seite 891 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Harding, Christian M [VerfasserIn] |
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| Links: |
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| Themen: |
Glycoproteins |
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| Anmerkungen: |
Date Completed 09.04.2019 Date Revised 09.03.2020 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-019-08869-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294174036 |
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| 100 | 1 | |a Harding, Christian M |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A platform for glycoengineering a polyvalent pneumococcal bioconjugate vaccine using E. coli as a host |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Pneumococcal Vaccines |2 NLM | |
| 650 | 7 | |a Vaccines, Conjugate |2 NLM | |
| 650 | 7 | |a Vaccines, Synthetic |2 NLM | |
| 700 | 1 | |a Nasr, Mohamed A |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Nichollas E |e verfasserin |4 aut | |
| 700 | 1 | |a Goyette-Desjardins, Guillaume |e verfasserin |4 aut | |
| 700 | 1 | |a Nothaft, Harald |e verfasserin |4 aut | |
| 700 | 1 | |a Mayer, Anne E |e verfasserin |4 aut | |
| 700 | 1 | |a Chavez, Sthefany M |e verfasserin |4 aut | |
| 700 | 1 | |a Huynh, Jeremy P |e verfasserin |4 aut | |
| 700 | 1 | |a Kinsella, Rachel L |e verfasserin |4 aut | |
| 700 | 1 | |a Szymanski, Christine M |e verfasserin |4 aut | |
| 700 | 1 | |a Stallings, Christina L |e verfasserin |4 aut | |
| 700 | 1 | |a Segura, Mariela |e verfasserin |4 aut | |
| 700 | 1 | |a Feldman, Mario F |e verfasserin |4 aut | |
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