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mRNA, DNA and vector vaccines: the modern platform technologies

Vaccines have really been around for a long time - in a wide variety of variants against a wide variety of pathogens. During a vaccination, you are given so-called antigens (viruses, bacteria, toxins or components of such), the immune system recognizes them as "foreign" and forms antibodies. When the real pathogen, the so-called wild type, appears, these antibodies identify it based on its shape and can eliminate it.

These antigens can be produced in different ways - you can inactivate whole viruses (e.g. TBE), you can inactivate and fragment them (e.g. influenza), you can only produce components of a pathogen using genetic engineering (e.g. hepatitis B), you can make pathogens weaken (attenuate) so that they can still multiply in the body, but can no longer make us sick (e.g. measles).

But what does “platform technologies” include?

mRNA vaccine

Our own body cells produce proteins. For comparison, let's imagine someone wants to build a house. To do this, you need a client who has the idea in mind of what the house should look like (DNA). So he draws a blueprint (mRNA) and the finished house is built based on the plan (protein). These processes are called transcription (translation of DNA into mRNA) and translation (translation of mRNA into a protein).

What happens with the mRNA vaccination? We give the cell an additional blueprint. Comparable to someone suggesting to the client: “Build another garage!” And handing them the plan for the garage (mRNA vaccine). And this garage looks exactly like the desired antigen (with the current COVID vaccines the so-called "spike" protein of the coronavirus) - a piece against which our immune system can form antibodies.

This structure of the protein based on the plan in the mRNA takes place outside the cell nucleus, so the mRNA does not come into contact with the DNA.

The molecular biologist Martin Moder made a great, short and easy to understand video about it.

Sometimes you hear that concerns are raised because such a vaccine has never made it through approval before. That's not right - it just hasn't been submitted yet. The current COVID vaccines are the first ever to be submitted for approval.

DNA vaccine

A DNA vaccine works - roughly in terms of its basic principle - in a similar way. In this case, the vaccinated person is given a plasmid - a circular piece of DNA that contains the genetic code for the desired antigen. This migrates into the cell nucleus and there the normal process of transcription takes place, as it otherwise takes place in the cell. Instead of receiving the finished blueprint as with the mRNA vaccine, the cell is given a second client and has to first draw the second blueprint and then build the antigen itself.

Plasmids are much more stable and resilient than RNA and are therefore easier to manufacture and store.

A DNA vaccine has been approved in Europe for several years: Clynav®, a vaccine for salmon against contagious pancreatitis.

The more ambitious among the readers can also read the public opinion on this vaccine.

This vaccine is mainly used in large salmon farms and injected intramuscularly into individual animals under anesthesia.

One advantage of DNA and RNA vaccines is purity. Since there is no need to isolate and cultivate a virus and no cell cultures are used, the risk of possible contamination with other viruses or other pathogens and the excessive test programs for these impurities that are normally required for vaccines are eliminated; the production is therefore much easier. The finished vaccines do not require an adjuvant and generally contain only a few ingredients.

Vector - vaccine

A conventional virus is used as the basis for vector vaccines (e.g. different adenoviruses, modified smallpox viruses (MVA) or weakened measles viruses are common in humans). The virus is modified using genetic engineering methods, which on the one hand is harmless to the vaccinated person and on the other hand carries the genetic code of the desired antigen.

That means: you use a non-pathogenic virus that infects the cell in the normal way, but which does not cause its own reproduction (as with a normal infection), but allows the cell to build the desired antigen. There are also vectors that lead the body to believe that they are actually a coronavirus. It does this by restructuring the vector virus so that it has proteins on its surface that make it look like a coronavirus.

Vector vaccines are already approved in both the human and veterinary sectors.

In the veterinary field there are some vector vaccines that can be used "twice": if the vaccine is to protect against 2 different diseases or against 2 different variants of the same virus, the vaccine virus, which then serves as an antigen and a vector at the same time, is the genetic one Code of the second virus and thus causes the cell to build the antigens for TWO viruses by means of infection by ONE virus.

In summary: the special thing about these three vaccine variants (mRNA, DNA, vector) is that the body does not receive the antigen (as we know it from conventional vaccines), but a blueprint for it - the cells of the vaccinated person or animal build it the desired antigen itself. The material introduced with the vaccine uses substances and mechanisms that are already present in the cell.

Protein-based vaccines - recombinant nanoparticles or virus-like particles

There are several different variants for this. Roughly described, it works in such a way that the desired antigen is produced using genetic engineering methods and coupled to a suitable protein or protein-lipid combination. In this case, the antigen is administered as with conventional vaccines, but in a highly purified form, since it only contains this specific antigen structure and no other parts of the virus. In the course of the work on COVID vaccines, some optimized processes were developed here, but the basic principle is not new, both in the human and in the veterinary field, such vaccines have been and are in use for a long time. They should only be mentioned here because they also belong to the platform technologies.

Why are these vaccine technologies mentioned here now called “platform technologies”?

In all of these ways of making vaccines, you have a basic manufacturing process that doesn't change - the so-called "platform". This means that the way in which mRNA, DNA plasmids, viral vectors ... are produced does not change, is consistent and always works in the same way. The genetic code for the desired antigen or, in the case of protein-based vaccines, the antigen itself can be exchanged. Changing just the sequence or antigen in question is much easier and faster than if you had to develop a completely new vaccine.

Such vaccines have long been under discussion both in the human and in the veterinary field, because they are seen as a way of quickly producing vaccines using well-established manufacturing processes, especially in all types of epidemic outbreaks in humans and animals. In principle, they also offer the technical option of reacting faster in the event of mutations.

In the currently widely discussed COVID vaccines, all 4 of the technologies mentioned are on board, although protein-based and DNA vaccines have not yet been submitted for approval (as of January 2021) If you are interested in COVID vaccines, you can read a lot here.

In the veterinary sector, work is currently underway on a new legal and regulatory - technical basis for the approval of such platforms; this can be read in the drafts of the new veterinary drug legislation, which will come into force in January 2022.

If you want to see which COVID vaccines are currently in work (worldwide), you can have a look here. Here you can find a list of the manufacturers concerned, what type of vaccine it is and what stage of development it is currently in.

And last but not least: I can warmly recommend this and this publication by the virologist Florian Krammer to the technically advanced readers for an overview of the COVID vaccine candidates.

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Posted byverdarenoPublished in General