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Effect of Shear Stresses on Adenovirus Activity and Aggregation during Atomization To Produce Thermally Stable Vaccines by Spray Drying

  • Blair A. Morgan
    Blair A. Morgan
    Department of Chemical Engineering, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
  • Myla Manser
    Myla Manser
    Department of Chemical Engineering, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
    More by Myla Manser
  • Mangalakumari Jeyanathan
    Mangalakumari Jeyanathan
    McMaster Immunology Research Centre and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
  • Zhou Xing
    Zhou Xing
    McMaster Immunology Research Centre and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
    More by Zhou Xing
  • Emily D. Cranston
    Emily D. Cranston
    Department of Chemical Engineering, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
    Department of Wood Science, University of British Columbia, 2424 Main Mall, Vancouver, V6T 1Z4 British Columbia, Canada
    Department of Chemical and Biological Engineering, University of British Columbia, 2360 East Mall, Vancouver, V6T 1Z3 British Columbia, Canada
  • , and 
  • Michael R. Thompson*
    Michael R. Thompson
    Department of Chemical Engineering, McMaster University, Hamilton, L8S 4L7 Ontario, Canada
    *Email: [email protected]
Cite this: ACS Biomater. Sci. Eng. 2020, 6, 7, 4304–4313
Publication Date (Web):June 1, 2020
https://doi.org/10.1021/acsbiomaterials.0c00317
Copyright © 2020 American Chemical Society

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    Abstract

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    Considering the substantive potential benefits of thermally stable dry powder vaccines to public health, causes for inactivation of their sensitive viral vectors during preparation require intensive study. The focus of this work was atomization of suspensions containing encapsulating excipients and a human type 5 adenovirus, involving a detailed investigation of shear stresses in the nozzle of a spray dryer. Samples were sprayed at 25 °C into falcon tubes and immediately evaluated for viral activity by in vitro testing, minimizing the confounding of thermal effects on the deactivation of the virus, although interfacial stresses could not be decoupled from shear stresses. Despite the expectations of only virus deactivation with ever-increasing shear stresses in the spray nozzle, some conditions were found to show better activity than the positive control, leading to investigations of viral aggregation. It was found that the adenovirus experienced minor aggregation when mixed with the excipient solutions, which was reversed by subjecting samples to moderate shear conditions in the spray nozzle. At very high shear rates, the activity diminished again because of damage to the viral capsid fibers, which also led to the production of new aggregates after atomization. Despite these findings, activity losses caused by shear were small compared to the overall spray drying process loss. However, formulation composition, solution viscosity, and process conditions should be considered carefully for optimization because of their impact on aggregation. This is the first known report comparing shear, aggregation, and biological activity loss during the atomization step of spray drying viral vaccines.

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    • Example for the live cell population, singlet cell population, and GFP-positive/-negative population gates applied to flow cytometry samples; standard curve used to analyze flow cytometry data; particle size distributions for the six samples; and mean and mode particle diameters for both 4 and 8% formulations (PDF)

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    11. Michael Y.T. Chow, Harry W. Pan, Han Cong Seow, Jenny K.W. Lam. Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections. Trends in Pharmacological Sciences 2023, 44 (2) , 85-97. https://doi.org/10.1016/j.tips.2022.11.006
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    13. Cordin Arpagaus. Conclusions and Future Perspectives of Spray-Dried Vaccines. 2023, 531-589. https://doi.org/10.1007/978-3-031-24323-3_7
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