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Corona Vaccine Development: Purification of COVID-19 Corona virus membrane proteins by detergents and hydrophobic beads.

The current crisis, caused by the new Corona virus “SARS-CoV-2” and the disease it causes named “coronavirus disease 2019” (abbreviated “COVID-19”) [1], asks for a quick but safe vaccine development program. The SARS-CoV-2 virus is a betacoronavirus, like MERS-CoV and SARS-CoV. [2]

Hoffmann et al. [3] report that the spike proteins of SARS-CoV-2 are involved in the infection and multiplication process of Corona viruses. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming. This mechanism of infection is similar to the Influenza virus, known from seasonal flu and H1N1 Mexican flu. [4]

The majority of Influenza vaccines are based on an egg-derived manufacturing process and they have a well-established purification process [5]. Although various types of vaccine are on the market, subunit vaccines do not contain live components and are considered as very safe [6]. Purification of the antigens Hemagglutinin and Neuraminidase is important as the removal of non-envelop proteins can contribute to low allergic reactions [6]. In the isolation and purification process of membrane proteins, surfactants like Trition-X100, CTAB, CHAPS, Polysorbate (Tween), Deoxycholate and other detergents are used. The selection for the detergent or a combination of detergents is important during the development phase of vaccines and can also be important in the development of a good manufacturing process. Detergents/surfactants can be very efficient in first solubilizing membrane (spike) proteins in a controlled way, and (in presence of phospholipids) formation of virosome like particles especially in combination with the use of sterile, ready to use hydrophobic beads like CCzorb-PGH4 [7].

As the new vaccine for SARS-CoV-2 must be accessible as soon as possible and probably will be provided to many people, it could be considered that the basis from a well-known manufacturing method for a high purity vaccine can be used. Even in combination with new technigues like computer-designed nanoparticles and protein building blocks.

Research groups are invited to apply for test samples of sterile, ready to use, hydrophobic beads of CCzorb-PG4H for controlled removal of detergents after solubilization of membrane proteins enabling formation of antigen presenting nanoparticles.

[1]       Centers for Disease Control and Prevention, Coronavirus Disease 2019 (COVID-19), Cases & Latest Updates

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/summary.html

[2]       World Health Organization, Health topics on Corona virus; https://www.who.int/health-topics/coronavirus

[3]       Hoffmann et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell (2020), https://doi.org/10.1016/j.cell.2020.02.052

[4]       Saunders-Hastings PR, Krewski D. Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission. Pathogens. 2016;5(4):66. Published 2016 Dec 6. doi:10.3390/pathogens5040066

[5]       Centers for Disease Control and Prevention, Seasonal Influenza (Flu), Prevent Flu,

https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm

[6]       WHO e-learning course

https://vaccine-safety-training.org/subunit-vaccines.html

[7]       CCzorb-PGH4®  Sterile Purified resins and cartridges, suitable for removal of detergents during vaccine production (e.g. Triton-X100, CTAB and Polysorbate 80)

http://rodiholding.nl/amberlite-resins/

photo   Health photo created by freepik https://www.freepik.com/free-photos-vectors/health

*          Author R. de Boer: https://www.linkedin.com/in/robert-de-boer-37712110/

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