Ultrasonics for Vaccine Production

Ultrasonics is a proven method to destroy or inactivate viruses, bacteria and yeast. Additionally, sonicators are reliable for the lysis of cells, e.g. viral or bacterial cells and the release of intracellular matter, e.g. proteins, DNA/RNA, enzymes and bioactives. Therefore, Hielscher sonicators are frequently used as reliable cell and virus treatment techniques during vaccine manufacturing. Subsequently, ultrasonic homogenisation is used to formulate solid-lipid nano-carriers or liposomes, whilst ultrasonic dispersion and deagglomeration are applied at various steps during vaccine production to obtain a homogeneous suspension.

Ultrasonic Vaccine Production

For the preparation of vaccines, including inactivated, attenuated, protein subunit or conjugate vaccines, cells have to be either inactivated, lysed or killed. With the appropriate dose and intensity of sonication, cells and microbes can be treated in accordance to the process goal.

Apply ultrasonic waves to:

• disrupt and lysate cells
• inactivate viral and bacterial cells
• release of intracellular material, e.g. proteins, antigens
• stimulate bacterial activity
• prepare nano drug carriers
• activate/ inactivate enzymes
• prepare nano-emulsions and double emulsions

More Applications of Sonicators in Vaccine Production

In vaccine production, Hielscher sonicators play a crucial role in various stages, including antigen production, encapsulation, formulation, and the essential degassing step prior to filling vaccines into vials or syringes.
 
Antigen Dispersion:
In order to achieve a stable vaccine formulation, it is imperative that antigens, such as cell fragments or protein antigens, are uniformly dispersed into suspensions, polymers, or liposomal encapsulations. Sonication has been a proven and long-standing technique in the manufacturing of pharmaceutical products, demonstrating its efficacy in preparing fine dispersions, making it an established tool in modern vaccine production.
 
Adjuvants:
Mixing and homogenization of adjuvants into vaccine formulations is reliably and efficiently achieved by sonication. One common type of adjuvant used in vaccine formulations is aluminum-based adjuvants, composed of tiny primary particles that can easily aggregate into a functional unit. For successful integration with antigens, a uniform distribution of antigens throughout the aluminum-containing vaccine is necessary. Ultrasonic dispersion serves this purpose by preparing homogeneous dispersions of antigens and adjuvants, such as Alhydrogel™.
 
Pathogen Inactivation:
Moreover, power ultrasound finds application in the inactivation of pathogens like bacteria and viruses. When it comes to preparing an effective colibacillosis vaccine, ultrasonic deactivation of E. coli, followed by irradiation, has been proven to be the most potent technique.
 
Microbial Inactivation and Stabilization:
Conventionally, microbial inactivation is achieved through thermal pasteurization and sterilization, which involve prolonged exposure to high temperatures, often leading to thermal-induced deterioration of functional properties. However, the combination of sonication and heat, known as thermo-sonication, offers a faster rate of sterilization with significantly reduced thermal intensity and duration. This is particularly advantageous for preserving heat-sensitive compounds, such as proteins and antigens. The process of ultrasonic sterilization and pasteurization is not only cost-efficient but also energy-saving and environmentally friendly.
 
Liposomes and Nanocarriers:
Hielscher sonicators are used to formulate drugs and vaccines into liposomes and nanostructured drug carriers such as solid-lipid nanoparticles. Sonication is an efficacious and reliable technique to encapsulate active ingredients into liposomes and nanoparticles. During ultrasonic encapsulation, precise control over the size of liposomes and nanocarriers is allowed, leading to a more consistent and uniform drug delivery system. Simultaneously, probe-type sonicators enable for enhanced drug loading: The mechanical forces generated during sonication aid in improving drug encapsulation efficiency, ensuring a higher amount of drug is incorporated into the carriers. with ultrasonic encapsulation comes also improved stability since sonication promotes the formation of stable liposomes and nanocarriers, which are essential for their successful application in vaccine delivery.
 

 

Find in-depth information and scientific studies on specific sonication-assited vaccine applications:

• Ultrasonic Solutions for Improved Vaccine Productio
• Nano-encapsulated Intranasal Vaccines
• Ultrasonic Lysis of Bioengineered Cells
• Drug Encapsulation into Lipid Nanoparticles
• Ultrasonic Treatment of Nanoparticles for Pharmaceuticals
• Sonicators for E. coli Lysis

Ultrasonic Vaccine Preparation on Lab and Industrial Scale

Hielscher Ultrasonics offers a broad range of ultrasonic devices from lab scale sonicators to full industrial-grade ultrasound homogenizers for commercial production. We cover your needs from small ultrasonicators for your research department up to the full-stream processing of your commercially produced pharmaceuticals.

Reliable and Adjustable to Your Application Needs

By adjusting the parameters of ultrasonic processing, the effects of sonication can be precisely controlled. This means that a low amplitude and short sonication has very soft effects, while high amplitudes, elevated pressure and longer sonication duration results in intense processing.
Hielscher supplies powerful ultrasonic devices that can be precisely controlled in accordance to the process requirements. Manifold sonotrodes and accessories complete the offering.

Safe and Clean

Hielscher ultrasonicators can be easily installed in cleanroom laboratories and production facilities. The housings of our devices are made from antibacterial plastic or stainless steel. All wetted parts, such as our sonotrodes and flow cells, are made from titanium or stainless steel and can be autoclaved.
Hielscher Ultrasonics offer a manifold range of standard probe-type sonicators and accessories as well as customized equipment.

Advantages

precisely adjustable to the process

clean & hygienic processing

highly reproducible

linear scale-up

easy & safe operation

reliable & robust equipment

high efficiency

 

 

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Literature/References

• Poinern, Gérrard Eddy Jai; Le, Xuan Thi; Shan, Songhua; Ellis, Trevor; Fenwick, Stan; Edwards, John; Fawcett, Derek (2011): Ultrasonic synthetic technique to manufacture a pHEMA nanopolymeric-based vaccine against the H6N2 avian influenza virus: a preliminary investigation. International Journal of Nanomedicine 6, 2011. 2167–2174
• Nico Böhmer, Andreas Dautel, Thomas Eisele, Lutz Fischer (2012): Recombinant expression, purification and characterisation of the native glutamate racemase from Lactobacillus plantarum NC8. Protein Expr Purif. 2013 Mar;88(1):54-60.
• Brandy Verhalen, Stefan Ernst, Michael Börsch, Stephan Wilkens (2012): Dynamic Ligand-induced Conformational Rearrangements in P-glycoprotein as Probed by Fluorescence Resonance Energy Transfer Spectroscopy. J Biol Chem. 2012 Jan 6;287(2): 1112-27.
• Zahra Hadian, Mohammad Ali Sahari, Hamid Reza Moghimi; Mohsen Barzegar (2014): Formulation, Characterization and Optimization of Liposomes Containing Eicosapentaenoic and Docosahexaenoic Acids; A Methodology Approach. Iranian Journal of Pharmaceutical Research (2014), 13 (2): 393-404.
• Han N.S., Basri M., Abd Rahman M.B. Abd Rahman R.N., Salleh A.B., Ismail Z. (2012): Preparation of emulsions by rotor-stator homogenizer and ultrasonic cavitation for the cosmeceutical industry. Journal of Cosmetic Science Sep-Oct; 63(5), 2012. 333-44.
• Raquel Martínez-González, Joan Estelrich, Maria Antònia Busquets (2016): Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI. International Journal of Molecular Science 2016.
• Shah Purvin, Parameswara Rao Vuddanda, Sanjay Kumar Singh, Achint Jain, Sanjay Singh (2014): Pharmacokinetic and Tissue Distribution Study of Solid Lipid Nanoparticles of Zidov in Rats. Journal of Nanotechnology, Volume 2014.
• Harshita Krishnatreyya, Sanjay Dey, Paulami Pal, Pranab Jyoti Das, Vipin Kumar Sharma, Bhaskar Mazumder (2019): Piroxicam Loaded Solid Lipid Nanoparticles (SLNs): Potential for Topical Delivery. Indian Journal of Pharmaceutical Education and Research Vol 53, Issue 2, 2019. 82-92.