Recombinant production platform for Group A Streptococcus glycoconjugate vaccines
Abstract Group A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydr...
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01068-2 |
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| author | Sowmya Ajay Castro Ian J. Passmore Didier Ndeh Helen Alexandra Shaw Alessandro Ruda Keira Burns Sarah Thomson Rupa Nagar Kathirvel Alagesan Mark Reglinski Kieron Lucas Sherif Abouelhadid Ulrich Schwarz-Linek Fatme Mawas Göran Widmalm Brendan W. Wren Helge C. Dorfmueller |
| author_facet | Sowmya Ajay Castro Ian J. Passmore Didier Ndeh Helen Alexandra Shaw Alessandro Ruda Keira Burns Sarah Thomson Rupa Nagar Kathirvel Alagesan Mark Reglinski Kieron Lucas Sherif Abouelhadid Ulrich Schwarz-Linek Fatme Mawas Göran Widmalm Brendan W. Wren Helge C. Dorfmueller |
| author_sort | Sowmya Ajay Castro |
| collection | DOAJ |
| description | Abstract Group A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydrate biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within Escherichia coli cells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates. |
| format | Article |
| id | doaj-art-a9901a2788a4441e8540f2131f900df4 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-a9901a2788a4441e8540f2131f900df42025-01-26T12:14:12ZengNature Portfolionpj Vaccines2059-01052025-01-0110111410.1038/s41541-025-01068-2Recombinant production platform for Group A Streptococcus glycoconjugate vaccinesSowmya Ajay Castro0Ian J. Passmore1Didier Ndeh2Helen Alexandra Shaw3Alessandro Ruda4Keira Burns5Sarah Thomson6Rupa Nagar7Kathirvel Alagesan8Mark Reglinski9Kieron Lucas10Sherif Abouelhadid11Ulrich Schwarz-Linek12Fatme Mawas13Göran Widmalm14Brendan W. Wren15Helge C. Dorfmueller16Division of Molecular Microbiology, School of Life SciencesDepartment of Infection Biology, London School of Hygiene and Tropical MedicineDivision of Molecular Microbiology, School of Life SciencesThe Medicines and Healthcare products Regulatory Agency (MHRA), Vaccines Division, Scientific Research & Innovation GroupDepartment of Organic Chemistry, Stockholm UniversityDepartment of Infection Biology, London School of Hygiene and Tropical MedicineBiological Services, School of Life Sciences, University of DundeeDivision of Molecular Microbiology, School of Life SciencesMax Planck Unit for the Science of PathogensDivision of Molecular Microbiology, School of Life SciencesDivision of Molecular Microbiology, School of Life SciencesDepartment of Infection Biology, London School of Hygiene and Tropical MedicineBiomedical Sciences Research Complex, University of St. AndrewsThe Medicines and Healthcare products Regulatory Agency (MHRA), Vaccines Division, Scientific Research & Innovation GroupDepartment of Organic Chemistry, Stockholm UniversityDepartment of Infection Biology, London School of Hygiene and Tropical MedicineDivision of Molecular Microbiology, School of Life SciencesAbstract Group A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydrate biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within Escherichia coli cells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates.https://doi.org/10.1038/s41541-025-01068-2 |
| spellingShingle | Sowmya Ajay Castro Ian J. Passmore Didier Ndeh Helen Alexandra Shaw Alessandro Ruda Keira Burns Sarah Thomson Rupa Nagar Kathirvel Alagesan Mark Reglinski Kieron Lucas Sherif Abouelhadid Ulrich Schwarz-Linek Fatme Mawas Göran Widmalm Brendan W. Wren Helge C. Dorfmueller Recombinant production platform for Group A Streptococcus glycoconjugate vaccines npj Vaccines |
| title | Recombinant production platform for Group A Streptococcus glycoconjugate vaccines |
| title_full | Recombinant production platform for Group A Streptococcus glycoconjugate vaccines |
| title_fullStr | Recombinant production platform for Group A Streptococcus glycoconjugate vaccines |
| title_full_unstemmed | Recombinant production platform for Group A Streptococcus glycoconjugate vaccines |
| title_short | Recombinant production platform for Group A Streptococcus glycoconjugate vaccines |
| title_sort | recombinant production platform for group a streptococcus glycoconjugate vaccines |
| url | https://doi.org/10.1038/s41541-025-01068-2 |
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