Recombinant production platform for Group A Streptococcus glycoconjugate vaccines

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

doi:10.1038/s41541-025-01068-2

Recombinant production platform for Group A Streptococcus glycoconjugate vaccines

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	16
Pages (from-to)	1-14
Number of pages	14
Journal	npj Vaccines
Volume	10
DOIs	https://doi.org/10.1038/s41541-025-01068-2
Publication status	Published - 22 Jan 2025

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Ajay Castro, S., Passmore, I. J., Ndeh, D., Shaw, H. A., Ruda, A., Burns, K., Thomson, S., Nagar, R., Alagesan, K., Reglinski, M., Lucas, K., Abouelhadid, S., Schwarz-Linek, U., Mawas, F., Widmalm, G., Wren, B. W., & Dorfmueller, H. C. (2025). Recombinant production platform for Group A Streptococcus glycoconjugate vaccines. npj Vaccines, 10, 1-14. Article 16. https://doi.org/10.1038/s41541-025-01068-2

@article{b6f1190efe9d45d09177c9d7de653f68,

title = "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 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.",

author = "\{Ajay Castro\}, Sowmya and Passmore, \{Ian J.\} and Didier Ndeh and Shaw, \{Helen Alexandra\} and Alessandro Ruda and Keira Burns and Sarah Thomson and Rupa Nagar and Kathirvel Alagesan and Mark Reglinski and Kieron Lucas and Sherif Abouelhadid and Ulrich Schwarz-Linek and Fatme Mawas and G{\"o}ran Widmalm and Wren, \{Brendan W.\} and Dorfmueller, \{Helge C.\}",

note = "Funding: The HCD laboratory is supported by Wellcome and Royal Society Grant 109357/Z/15/Z, the University of Dundee Wellcome Trust Funds 105606/Z/14/Z. The HCD and BWW laboratories are supported by Wellcome Innovator Award 221589/Z/20/Z and RIGHT Foundation grant RF-2023-V02. The GW laboratory was supported by grants from the Swedish Research Council (2022-03014) and the Knut and Alice Wallenberg Foundation. KA is supported by the Max Planck Society. HAS, FM are funded by Wellcome Innovator Award 221589/Z/20/Z, and independent research commissioned and funded by the NIHR Policy Research Programme (NIBSC Regulatory Science Research Unit). ",

year = "2025",

month = jan,

day = "22",

doi = "10.1038/s41541-025-01068-2",

language = "English",

volume = "10",

pages = "1--14",

journal = "npj Vaccines",

issn = "2059-0105",

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}

Ajay Castro, S, Passmore, IJ, Ndeh, D, Shaw, HA, Ruda, A, Burns, K, Thomson, S, Nagar, R, Alagesan, K, Reglinski, M, Lucas, K, Abouelhadid, S, Schwarz-Linek, U, Mawas, F, Widmalm, G, Wren, BW & Dorfmueller, HC 2025, 'Recombinant production platform for Group A Streptococcus glycoconjugate vaccines', npj Vaccines, vol. 10, 16, pp. 1-14. https://doi.org/10.1038/s41541-025-01068-2

TY - JOUR

T1 - Recombinant production platform for Group A Streptococcus glycoconjugate vaccines

AU - Ajay Castro, Sowmya

AU - Passmore, Ian J.

AU - Ndeh, Didier

AU - Shaw, Helen Alexandra

AU - Ruda, Alessandro

AU - Burns, Keira

AU - Thomson, Sarah

AU - Nagar, Rupa

AU - Alagesan, Kathirvel

AU - Reglinski, Mark

AU - Lucas, Kieron

AU - Abouelhadid, Sherif

AU - Schwarz-Linek, Ulrich

AU - Mawas, Fatme

AU - Widmalm, Göran

AU - Wren, Brendan W.

AU - Dorfmueller, Helge C.

N1 - Funding: The HCD laboratory is supported by Wellcome and Royal Society Grant 109357/Z/15/Z, the University of Dundee Wellcome Trust Funds 105606/Z/14/Z. The HCD and BWW laboratories are supported by Wellcome Innovator Award 221589/Z/20/Z and RIGHT Foundation grant RF-2023-V02. The GW laboratory was supported by grants from the Swedish Research Council (2022-03014) and the Knut and Alice Wallenberg Foundation. KA is supported by the Max Planck Society. HAS, FM are funded by Wellcome Innovator Award 221589/Z/20/Z, and independent research commissioned and funded by the NIHR Policy Research Programme (NIBSC Regulatory Science Research Unit).

PY - 2025/1/22

Y1 - 2025/1/22

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85217773997

U2 - 10.1038/s41541-025-01068-2

DO - 10.1038/s41541-025-01068-2

M3 - Article

SN - 2059-0105

VL - 10

SP - 1

EP - 14

JO - npj Vaccines

JF - npj Vaccines

M1 - 16

ER -

Recombinant production platform for Group A Streptococcus glycoconjugate vaccines

Abstract

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