Increasing vaccine production using pulsed ultrasound waves

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.

Noninvasive focused ultrasound non-specifically activating spleen immunological function to suppress tumor proliferation: a new strategy for cancer immunotherapy

“…Moreover, MHC class II protein complex was suppressed (Figure 8 F), which promoted NK cell activation in mice as reported by Li Y. et al [70]. Particularly, KEGG enrichment analysis of these upregulated genes showed the upregulation of PI3K-Akt signaling pathway, Hippo signaling pathway, ErbB signaling pathway, and Ras signaling pathway (Figure 8 G), which were closely associated with cell proliferation, differentiation and activation, especially under ultrasound stimulation [71][72][73]. Downregulated genes were signi cantly enriched in the intestinal immune network for IgA production (Figure 8 H), which might be bene cial to tumor suppression as previous studies reported that IgA inhibits NK activity of NK cellenriched lymphoid cells and gamma-interferon-treated effector cells [74,75].…”

Ultrasound-assisted magnetic nanoparticle-based gene delivery

“…In this paper, we combined both physical and chemical approaches to develop a high-efficient gene delivery method with low-cytotoxicity. From the previous work done in our group as well as by other groups and reported in the literature, we knew that LIPUS could transiently increase cell membrane permeability [ 31 ] as well as can be beneficial for cell viability [ 35 , 43 ]. Our goal was to evaluate whether ultrasound can enhance the entry of genes into the cells when used with MNPs as a transfection tool.…”

“…Different ultrasound parameters, such as wave intensity, treatment duration, and frequency of the treatment, can have a significantly different effect on the cell growth and membrane permeability [31,35]. Therefore, we needed to select the optimal conditions of the LIPUS stimulation for our studies.…”

“…Using graphene aerogel to promote cell proliferation was reported [ 29 , 30 ]. LIPUS has also been proven to help division and proliferation in many types of cells, such as insect cells [ 31 ], algal cells [ 32 ], stem/progenitor cell [ 33 ], mesenchymal stromal cells [ 34 ]. LIPUS can also increase CHO cell growth and antibody production [ 35 ], increase cell permeability [ 31 ], and enhance gene delivery by using microbubble [ 36 ].…”