Modern Vaccines and Platform Technologies - Explained in an Understandable Way

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7/8 May 2024

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Regulatory Requirements and Practical Implementation

In the current situation, we receive a variety of questions about the current vaccine development, vaccine types, licensure and more. Therefore, we have compiled some general available information and the comments of experienced ECA members and expert speakers in such a way that one or the other question is answered:

Background

As far as the production of vaccines is concerned, we already have decades of experience. In the course of time, a wide variety of vaccines have been developed against a wide variety of pathogens. During vaccination, the patient is administered so-called antigens (viruses, bacteria, toxins or components of such), the body's own immune system recognizes these as "foreign" and forms corresponding antibodies. If the real pathogen, the so-called wild type, then enters the body, these antibodies identify it on the basis of its molecular biological shape and can thus eliminate it.

These antigens can be produced in various ways - entire viruses can be inactivated (e.g. TBE), they can be inactivated and fragmented (e.g. influenza), genetic engineering methods can be used to produce only components of a pathogen (e.g. hepatitis B), pathogens can be weakened (attenuated) so that they can still multiply in the body but can no longer make us ill (e.g. measles).

But what are the so-called "platform technologies" that we are currently reading and hearing so much about?

The new weapon - mRNA vaccines

Our own body cells produce proteins. To understand how this happens, we can use a comparison, for example the building of a house. To do this, we need a builder who has an idea of what the house should look like (DNA). So the builder draws a blueprint (mRNA). Based on this blueprint the house is built (protein). These processes are called transcription (translation of DNA into mRNA in the cell nucleus) and translation (translation of mRNA into a protein at/with the ribosomes, outside the cell nucleus).

What happens during mRNA inoculation? We give our cells an additional blueprin - comparable to building a garage for the house and providing the plan for this garage (mRNA - vaccine/virus protein). And this garage looks exactly like the desired antigen (in the current COVID - vaccines the so-called "spike" - protein of the coronavirus) - a piece against which our immune system can form antibodies.

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

Sometimes there are concerns expressed because such a vaccine has never made been approved before. This is not true - it is just that none has been submitted so far. The current COVID vaccines are the first ever to be filed or approved.

However, mRNA is not that stable and degrades quite rapidly in the cell. For this reason, it is often "packaged" for introduction into the cell, i.e. it is given an envelope, a "liposome". To keep this stable during storage and transport, low temperatures may be necessary.

DNA Vaccines

A DNA vaccine works in a similar way in terms of its basic principle. In this case, the vaccinated person receives a so-called plasmid - a ring-shaped piece of DNA that contains the genetic code for the desired antigen (virus protein). This migrates into the cell nucleus, where the normal process of transcription takes place, just as it does in the cell. Instead of receiving the finished blueprint immediately, as is the case with the mRNA vaccine, the cell receives a second builder, so to speak, and must first draw the second blueprint itself on the basis of its information and then, outside the cell nucleus, build the antigen itself with the building tools and building blocks.

Plasmids are much more stable and resistant than RNA and therefore easier to produce and store.

A DNA vaccine has been approved in Europe for several years: Clynav®, a vaccine for salmon against contagious pancreatitis.
This vaccine is mainly used in large salmon farms and is inoculated by intramuscular injection on the individual animal, under anesthesia.

One advantage of DNA and RNA vaccines is their purity. Since no virus has to be isolated and grown and no cell cultures are used, the risk of possible contamination with other viruses, other pathogens or cell residues and the extensive testing programs for these very contaminants normally required for vaccines are eliminated. This simplifies production The finished vaccines do not require an adjuvant and generally contain few ingredients.

Vector Vaccines

Vector vaccines are based on an already known virus. For human vaccines, for example, various adenoviruses, modified smallpox viruses (MVA) or attenuated measles viruses are used. These known viruses are genetically modified so that they are harmless to the vaccinated person and carry the required genetic information for the desired antigen. This means that when it enters the cell, i.e. "infects" it, it no longer initiates its own replication by the host cell, but instead the desired antigen is produced. Alternatively, the vector virus can be modified so that it carries the desired antigen, e.g. the protein of a coronavirus, on its surface. Then the body mistakes it for a coronavirus and produces appropriate antibodies.

Vector vaccines are already approved in both human and veterinary settings.

In the veterinary field, there are some vector vaccines that can be used "twice": if the vaccine is to protect against two different diseases or against two different variants of the same virus, the genetic code of the second pathogen is added to the vaccine virus and thus causes the cell to build the antigens for TWO viruses by means of infection by ONE virus.

In summary, the special feature of these three vaccine variants (mRNA, DNA, vector) is that the body is not administered the antigen (as we know it from conventional vaccines), but a blueprint for it - the cells of the vaccinated human or animal thus build the desired antigen themselves. The material introduced with the vaccine uses substances and mechanisms that are present in the cell anyway.

Protein-Based Vaccines - recombinant nanoparticles or virus-like particles

There are several different variants for this. Simply described, it works by producing the desired antigen by genetic engineering methods and coupling it to a suitable protein or protein-lipid combination. In this case, the antigen is administered as in conventional vaccines, but in a highly purified form, since only this specific antigenic structure is contained and no other virus parts. In the course of the work on COVID vaccines, some optimized procedures have been developed, but the basic principle itself is not new; such vaccines have been in use for a long time in both the human and veterinary fields. 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 these ways of producing vaccines, one has a basic manufacturing process that does not change - the so-called "platform". That is, the way mRNA, DNA - plasmids, viral vectors, etc. are made does not change. It is consistent and always works the same way. However, the genetic code for the desired antigen or, in the case of protein-based vaccines, the antigen itself can be exchanged. Such a change of only the sequence or antigen in question is much simpler and much faster than having to develop a complete vaccine from scratch.

Such vaccines have therefore been under discussion for a long time in both the human and veterinary sectors, because they are seen as a way of rapidly producing vaccines on the basis of well-established manufacturing processes, especially in the case of all kinds of disease outbreaks in humans and animals. In principle, they also offer the technical possibility of reacting more quickly in the event of mutations.

Current Status

In the current development and production of COVID-19 vaccines, all of these technologies are in use, although protein-based and DNA vaccines are currently (early January) not yet submitted for approval. Technical considerations and assessments of the approvals for these vaccines can also be found at "EMA considerations on COVID-19 vaccine approval" and the WHO provides a tracker for current developments at "Draft landscape and tracker of COVID-19 candidate vaccines". Further publications on the SARS-CoV-2 vaccines can be found at
"SARS-CoV-2 Vaccines: Status Report" by Amanat and Kammer and "SARS-CoV-2 vaccines in development" by Kammer.