COVID-19: Search for a vaccine by Patric U. B. Vogel

Author:Patric U. B. Vogel
Language: eng
Format: epub
ISBN: 9783658389314
Publisher: Springer Fachmedien Wiesbaden

4.2 Recombinant Proteins (Protein Subunits)

The subunit vaccines (hereinafter referred to as proteins) presented in Sect. 4.1 can be produced not only from inactivated viruses, but also with the aid of biotechnological methods (= recombinant). In this process, the genetic sequence for the desired protein or part of the protein is inserted into certain DNA molecules, so-called plasmids. Plasmids are independent genetic elements (ring-shaped DNA molecules) that can replicate in cells. Plasmids are also used, for example, by bacteria to exchange antibiotic resistance, which can lead to multidrug-resistant bacteria. These plasmid DNA molecules are now multiplied. This is done by introducing them into cells such as the classic baker’s yeast, Saccharomyces cerevisae, or bacteria such as Escherichia coli. These organisms divide quickly and can be multiplied in large masses, in so-called fermenters. These fermenters are large tanks filled with nutrient fluid in which the growth conditions can be optimally controlled. The plasmids, just like the DNA of the cells, are passed on to the daughter cells with each cell division. In the end, you have a large biomass of cells that all have plasmids with the information for, for example, the spike protein of SARS-CoV-2. Using the genetic information of the plasmids, this recombinant SARS-CoV-2 protein is formed in the cells. After fermentation is complete, the proteins are separated and purified from the cells and other components, and finally adjuvants are added. This means that although the production process of inactivated (Sect. 4.1) and recombinant proteins is completely different, both require adjuvants to activate the immune system sufficiently. Hepatitis B is an example of a recombinant protein vaccine that is regularly used in humans. One advantage of recombinant proteins is the lower biosafety level, as the virus does not need to be replicated.

According to the WHO, most vaccine projects against COVID-19, about one third, are based on protein vaccines (WHO 2020a). This underlines how quickly these established biotechnological processes can be applied to new viruses. Already 20 candidates are in various clinical phases. As a caveat, a single protein is not necessarily as effective against a disease as classical vaccines. Of course, there are particularly immunogenic regions of a protein, called epitopes, in every virus, but the holistic immune response against whole viruses is usually directed against different proteins and here again different epitopes. Recombinant proteins therefore tend to have lower immunogenicity compared to traditional whole virus vaccines (Karch and Burkhard 2016). For this reason, improvements in this area are the focus of intensive research efforts. One way to improve the immunogenicity of protein vaccines is through nanoparticle technology, such as coating nanoparticles with the proteins (Pati et al. 2018). The news on the first candidate approved in Russia, EpiVacCorona, which is considered to have 100% efficacy, is very good, although the publication of the data is still pending. Russia has already announced mass production of this vaccine (ärzteblatt.de 2021). For the EU, another option is the product NVX-CoV2373 from the company Novavax, which is in the approval phase in the EU.

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