Increasing vaccine production using pulsed ultrasound waves

PLoS One. 2017 Nov 27;12(11):e0187048. doi: 10.1371/journal.pone.0187048. eCollection 2017.

Abstract

Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein production. In order to prove this hypothesis, Sf9 insect cells were used to evaluate the increase in the expression of a fusion protein from hepatitis B virus (HBV S1/S2). We discovered that the ultrasound stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day increased HBV S1/S2 by 27%. We further derived a model for transport through a cell membrane under the effect of ultrasound waves, tested the key assumptions of the model through a molecular dynamics simulation package, NAMD (Nanoscale Molecular Dynamics program) and utilized CHARMM force field in a steered molecular dynamics environment. The results show that ultrasound waves can increase cell permeability, which, in turn, can enhance nutrient / waste exchange thus leading to enhanced vaccine production. This finding is very meaningful in either shortening vaccine production time, or increasing the yield of proteins for use as vaccines.

MeSH terms

  • 4-Chloro-7-nitrobenzofurazan / analogs & derivatives
  • 4-Chloro-7-nitrobenzofurazan / metabolism
  • Animals
  • Blotting, Western
  • Cell Membrane Permeability
  • Deoxyglucose / analogs & derivatives
  • Deoxyglucose / metabolism
  • Hepatitis B Vaccines / biosynthesis*
  • Hepatitis B Vaccines / immunology
  • Molecular Dynamics Simulation
  • Phosphatidylcholines / chemistry
  • Proteins / metabolism
  • Sf9 Cells
  • Sonication
  • Thermodynamics
  • Ultrasonic Waves*

Substances

  • Hepatitis B Vaccines
  • Phosphatidylcholines
  • Proteins
  • Deoxyglucose
  • 1,2-oleoylphosphatidylcholine
  • 4-Chloro-7-nitrobenzofurazan
  • 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose

Grants and funding

The funder (The Natural Sciences and Engineering Research Council of Canada (NSERC)) provided support in the form of salaries for the graduate student, Mr. Jida Xing, and research materials but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.