Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN

Research output: Contribution to journalJournal articleResearchpeer-review

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Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN. / Rose, Fabrice; Roovers, Silke; Fano, Mathias; Harloff-Helleberg, Stine; Kirkensgaard, Jacob J K; Hejnaes, Kim; Fischer, Per; Foged, Camilla.

In: Molecular Pharmaceutics, Vol. 15, 2018, p. 2584-2593.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rose, F, Roovers, S, Fano, M, Harloff-Helleberg, S, Kirkensgaard, JJK, Hejnaes, K, Fischer, P & Foged, C 2018, 'Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN', Molecular Pharmaceutics, vol. 15, pp. 2584-2593. https://doi.org/10.1021/acs.molpharmaceut.8b00101

APA

Rose, F., Roovers, S., Fano, M., Harloff-Helleberg, S., Kirkensgaard, J. J. K., Hejnaes, K., ... Foged, C. (2018). Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN. Molecular Pharmaceutics, 15, 2584-2593. https://doi.org/10.1021/acs.molpharmaceut.8b00101

Vancouver

Rose F, Roovers S, Fano M, Harloff-Helleberg S, Kirkensgaard JJK, Hejnaes K et al. Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN. Molecular Pharmaceutics. 2018;15:2584-2593. https://doi.org/10.1021/acs.molpharmaceut.8b00101

Author

Rose, Fabrice ; Roovers, Silke ; Fano, Mathias ; Harloff-Helleberg, Stine ; Kirkensgaard, Jacob J K ; Hejnaes, Kim ; Fischer, Per ; Foged, Camilla. / Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN. In: Molecular Pharmaceutics. 2018 ; Vol. 15. pp. 2584-2593.

Bibtex

@article{4d5059993f924bcfad097eeb07991b6e,
title = "Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN",
abstract = "Group B Streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials. Understanding the physical stability of GBS-NN containing conformational B-cell epitopes is crucial to ensure optimal vaccine stability, efficacy, and safety. We initially discovered that GBS-NN is prone to form higher-order structures at elevated temperatures. We therefore investigated the self-assembly behavior of GBS-NN and characterized the higher-order conformational structures as a function of temperature. In the native state, GBS-NN exists as a monomer and has a secondary structure containing α-helix and β-sheet. Langmuir studies demonstrated that the native protein is highly surface-active and forms a monolayer film at the air-water interface because of its amphipathic properties. The conformational stability of GBS-NN was measured as a function of temperature. GBS-NN has an unusual thermal behavior with a phase transition of approximately 61 °C, which is not accompanied by any major changes in the secondary structure. However, the antigen showed irreversible self-assembly as a function of temperature into higher-order structures with a hydrodynamic diameter of approximately 100 nm. Cryo-transmission electron microscopy analyses demonstrated that these self-assemblies consist of vesicular, ring-like structures with a hollow aqueous interior. Therefore, GBS-NN is a physically stable monomeric protein but is prone to temperature-induced self-assembly above 61 °C.",
author = "Fabrice Rose and Silke Roovers and Mathias Fano and Stine Harloff-Helleberg and Kirkensgaard, {Jacob J K} and Kim Hejnaes and Per Fischer and Camilla Foged",
year = "2018",
doi = "10.1021/acs.molpharmaceut.8b00101",
language = "English",
volume = "15",
pages = "2584--2593",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Temperature-Induced Self-Assembly of the Group B Streptococcus (GBS) Fusion Antigen GBS-NN

AU - Rose, Fabrice

AU - Roovers, Silke

AU - Fano, Mathias

AU - Harloff-Helleberg, Stine

AU - Kirkensgaard, Jacob J K

AU - Hejnaes, Kim

AU - Fischer, Per

AU - Foged, Camilla

PY - 2018

Y1 - 2018

N2 - Group B Streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials. Understanding the physical stability of GBS-NN containing conformational B-cell epitopes is crucial to ensure optimal vaccine stability, efficacy, and safety. We initially discovered that GBS-NN is prone to form higher-order structures at elevated temperatures. We therefore investigated the self-assembly behavior of GBS-NN and characterized the higher-order conformational structures as a function of temperature. In the native state, GBS-NN exists as a monomer and has a secondary structure containing α-helix and β-sheet. Langmuir studies demonstrated that the native protein is highly surface-active and forms a monolayer film at the air-water interface because of its amphipathic properties. The conformational stability of GBS-NN was measured as a function of temperature. GBS-NN has an unusual thermal behavior with a phase transition of approximately 61 °C, which is not accompanied by any major changes in the secondary structure. However, the antigen showed irreversible self-assembly as a function of temperature into higher-order structures with a hydrodynamic diameter of approximately 100 nm. Cryo-transmission electron microscopy analyses demonstrated that these self-assemblies consist of vesicular, ring-like structures with a hollow aqueous interior. Therefore, GBS-NN is a physically stable monomeric protein but is prone to temperature-induced self-assembly above 61 °C.

AB - Group B Streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials. Understanding the physical stability of GBS-NN containing conformational B-cell epitopes is crucial to ensure optimal vaccine stability, efficacy, and safety. We initially discovered that GBS-NN is prone to form higher-order structures at elevated temperatures. We therefore investigated the self-assembly behavior of GBS-NN and characterized the higher-order conformational structures as a function of temperature. In the native state, GBS-NN exists as a monomer and has a secondary structure containing α-helix and β-sheet. Langmuir studies demonstrated that the native protein is highly surface-active and forms a monolayer film at the air-water interface because of its amphipathic properties. The conformational stability of GBS-NN was measured as a function of temperature. GBS-NN has an unusual thermal behavior with a phase transition of approximately 61 °C, which is not accompanied by any major changes in the secondary structure. However, the antigen showed irreversible self-assembly as a function of temperature into higher-order structures with a hydrodynamic diameter of approximately 100 nm. Cryo-transmission electron microscopy analyses demonstrated that these self-assemblies consist of vesicular, ring-like structures with a hollow aqueous interior. Therefore, GBS-NN is a physically stable monomeric protein but is prone to temperature-induced self-assembly above 61 °C.

U2 - 10.1021/acs.molpharmaceut.8b00101

DO - 10.1021/acs.molpharmaceut.8b00101

M3 - Journal article

C2 - 29745668

VL - 15

SP - 2584

EP - 2593

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

ER -

ID: 198602170