Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine
Purpose: The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. Methods: Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of nove...
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doaj-66d02d0a692647a7818df298c6e5436d2021-01-08T04:19:22ZengElsevierComputational and Structural Biotechnology Journal2001-03702021-01-0119439447Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccineJessica Duprez0Kristen Kalbfleisch1Sasmit Deshmukh2Jessie Payne3Manjit Haer4Wayne Williams5Ibrahim Durowoju6Marina Kirkitadze7Analytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, Canada; Department of Biology, York University, 4700 Keele Street, Toronto, Ontario, CanadaDepartment of Physiology & Pharmacology, and Paediatrics, University of Calgary, 2500 University Drive NW, Calgary, Alberta, CanadaSGS Canada, Biopharmaceutical Services, 6490 Vipond Drive, Mississauga, Ontario, CanadaAnalytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, CanadaAnalytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, CanadaAnalytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, CanadaAnalytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, CanadaAnalytical Sciences, Sanofi Pasteur Canada, 1755 Steeles Avenue West, Toronto, Ontario, Canada; Corresponding author.Purpose: The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. Methods: Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of novel gdPT and the composition of AlOOH adjuvant formulations adsorbed to pertussis vaccine. Results: DLS particle size results were 9.3 nm and 320 nm for gdPT. For pertussis toxoid (PT), the DLS particle size results were larger at ~440 nm. After adsorption to AlOOH, which was driven by the protein antigen, the size distribution ranged from 3.5 to 22 µm. Two thermal transitions were observed by DSC for gdPT at 70 °C and 102 °C. The main thermal transition was confirmed to be at 72 °C by nanoDSF. All three vaccine formulations showed one thermal transition: Tdap-AlOOH had a thermal transition of 74.6 °C, Tdap-E6020-AlOOH had a thermal transition at 74.2 °C, and Tdap-CpG-AlOOH had a thermal transition at 77.0 °C. Analysis of pertussis toxin (PTx) and gdPT was also performed by FTIR spectroscopy for the purpose of comparison. The second derivative of the FTIR spectra showed an additional feature for PTx at 1685 cm−1 compared to gdPT. The antigen’s amide I and II regions were largely unchanged after adsorption to AlOOH adjuvant as shown by FTIR, suggesting that there were no significant changes in the secondary structure. Conclusion: gdPT conformation was successfully characterized using an array of analytical methods. All three Tdap formulations have similar thermal stability as shown by nanoDSF, similar size distribution as shown by LD, and similar overall secondary structure as shown by FTIR. In-line particle sizing and IR can be used as in-process characterization tools to monitor consistency of adsorbed vaccine and to confirm product identity.http://www.sciencedirect.com/science/article/pii/S2001037020305481PertussisTdap vaccinesTLR agonistParticle sizingFTIRPAT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jessica Duprez Kristen Kalbfleisch Sasmit Deshmukh Jessie Payne Manjit Haer Wayne Williams Ibrahim Durowoju Marina Kirkitadze |
spellingShingle |
Jessica Duprez Kristen Kalbfleisch Sasmit Deshmukh Jessie Payne Manjit Haer Wayne Williams Ibrahim Durowoju Marina Kirkitadze Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine Computational and Structural Biotechnology Journal Pertussis Tdap vaccines TLR agonist Particle sizing FTIR PAT |
author_facet |
Jessica Duprez Kristen Kalbfleisch Sasmit Deshmukh Jessie Payne Manjit Haer Wayne Williams Ibrahim Durowoju Marina Kirkitadze |
author_sort |
Jessica Duprez |
title |
Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
title_short |
Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
title_full |
Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
title_fullStr |
Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
title_full_unstemmed |
Structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
title_sort |
structure and compositional analysis of aluminum oxyhydroxide adsorbed pertussis vaccine |
publisher |
Elsevier |
series |
Computational and Structural Biotechnology Journal |
issn |
2001-0370 |
publishDate |
2021-01-01 |
description |
Purpose: The goal of this study was to characterize an acellular pertussis vaccine (Tdap) containing genetically modified pertussis toxin (gdPT) and TLR agonist adsorbed to AlOOH adjuvant. Methods: Several analytical tools including nanoDSF, FTIR, and LD were used to examine the conformation of novel gdPT and the composition of AlOOH adjuvant formulations adsorbed to pertussis vaccine. Results: DLS particle size results were 9.3 nm and 320 nm for gdPT. For pertussis toxoid (PT), the DLS particle size results were larger at ~440 nm. After adsorption to AlOOH, which was driven by the protein antigen, the size distribution ranged from 3.5 to 22 µm. Two thermal transitions were observed by DSC for gdPT at 70 °C and 102 °C. The main thermal transition was confirmed to be at 72 °C by nanoDSF. All three vaccine formulations showed one thermal transition: Tdap-AlOOH had a thermal transition of 74.6 °C, Tdap-E6020-AlOOH had a thermal transition at 74.2 °C, and Tdap-CpG-AlOOH had a thermal transition at 77.0 °C. Analysis of pertussis toxin (PTx) and gdPT was also performed by FTIR spectroscopy for the purpose of comparison. The second derivative of the FTIR spectra showed an additional feature for PTx at 1685 cm−1 compared to gdPT. The antigen’s amide I and II regions were largely unchanged after adsorption to AlOOH adjuvant as shown by FTIR, suggesting that there were no significant changes in the secondary structure. Conclusion: gdPT conformation was successfully characterized using an array of analytical methods. All three Tdap formulations have similar thermal stability as shown by nanoDSF, similar size distribution as shown by LD, and similar overall secondary structure as shown by FTIR. In-line particle sizing and IR can be used as in-process characterization tools to monitor consistency of adsorbed vaccine and to confirm product identity. |
topic |
Pertussis Tdap vaccines TLR agonist Particle sizing FTIR PAT |
url |
http://www.sciencedirect.com/science/article/pii/S2001037020305481 |
work_keys_str_mv |
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