How does the UK Approved COVID-19 vaccine work?

Synthetic Biology Technology has brought us to the point today that the UK has accepted one of the COVID-19 vaccines for distribution, with the promise that distribution will begin soon. This result has taken just 10 months, how have the pharmaceutical researchers managed to do this? Through advances in technology.

In reality, there are different types of COVID-19 vaccine currently in trials:

1: Live attenuated vaccines

Some well-known vaccines for other infectious diseases are based on weakened versions of a virus.  These are known as live attenuated vaccines.
The viruses are weakened to reduce virulence by culturing cells in a laboratory, and then processed into a vaccine. After people come into contact with these attenuated viruses through vaccination, the virus will not be able to replicate easily in humans. As a result, our immune system has enough time to learn how to fight against this weaker form of the virus. This approach enables us to become immune without getting sick.

2: Inactivated vaccines

Inactivated vaccines contain viruses or bacteria that have been killed, which are either whole or in pieces. When our immune system detects these dead viruses or bacteria or their fragments, it can learn to recognise the fragments. After this, we are protected. If we are infected by the live version of the virus or bacteria in the future, our immune system will recognise the virus or bacteria and respond more quickly to protect us from infection – so we will not become ill.

3: Subunit vaccines

If the vaccine only contains particular pieces of a virus or bacteria, it is known as a subunit vaccine. When that subunit can be recognised by the immune system, it is referred to as an antigen.
Extensive research is being carried out on subunit vaccines for protection against COVID-19. An important subunit of SARS-CoV-2 is the spike protein or S protein, which is attached to the exterior of the virus. The virus uses the S protein to make contact with another protein which is located on the exterior of the cells in our lung vesicles. If the virus attaches itself to a human cell via the S protein, the virus can penetrate the exterior and enter the cell. Then the cell is infected.  Because the S protein plays such an essential role in the infection process, it is targeted by many vaccine developers. If we are infected by the live version of the virus in the future, our immune system will immediately recognise the virus and we will not become ill.

4: mDNA and mRNA vaccines (m stands for messenger)

DNA and RNA vaccines add a new piece of genetic material – deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) – to specific immune cells in our body. The targeted cells are often a particular type, which absorb and break down a virus or bacteria. The immune cells that have broken down a virus or bacteria then show a piece of the virus or bacteria (a subunit known as an antigen) to other immune cells so they learn to recognize the antigen. That is why these immune cells are also referred to as antigen-presenting cells. The cells that learn to recognize the antigen are called lymphocytes. DNA and RNA vaccines allow the antigen-presenting cells to detect a piece of the pathogen without the cell first having to absorb and break down the live version of the virus or bacteria. If we are then infected by the live version of the virus or bacteria in the future, the lymphocytes will recognize the antigen for the pathogen, neutralize the virus or bacteria, and we will not become ill.

There are also DNA and RNA vaccines that use ‘normal’ body cells instead of immune cells. These cells also present the antigen to our immune system, which ensures that we will not become ill if we do get infected. 
These DNA and RNA techniques are new, and a DNA or RNA vaccine has not yet been approved for any human disease. A number of DNA vaccines have already been used successfully for animals.

5: Vector vaccines

Researchers can modify existing viruses to act as vaccines. Once that happens, they are no longer viruses, but vectors. The viruses have been adapted in such a way that they do not display exactly the same behaviour as unmodified viruses. The difference compared to the real viruses is that vector viruses:

  • can no longer make someone ill;
  • (often) cannot replicate themselves, and;
  • not only contain their own RNA or DNA, but also have a piece of RNA or DNA from another virus within them. All pieces of RNA or DNA can work as an antigen, so the cells in our immune system will react to the vector virus as well as to part of the vaccine virus. This is how immunity is developed.

A category of viruses that are often adapted into a vector are the adenoviruses. Adenoviruses are a group of viruses to which people are often exposed, but which cause no or only mild illness. Because adenoviruses are so common, our immune system is very good at dealing with an adenovirus infection.

This article in Nature goes into further detail.

The vaccine approved today in the UK from Pfizer/BioNTech is an mRNA vaccine. This is cutting-edge technology, and the first time such a vaccine has been approved!

To produce an mRNA vaccine, scientists produce a synthetic version of the mRNA that a virus uses to build its infectious proteins. This mRNA is delivered into the human body, whose cells read it as instructions to build that viral protein, and therefore create some of the virus’s molecules themselves. These proteins are solitary, so they do not assemble to form a virus. The immune system then detects these viral proteins and starts to produce a defensive response to them.

Synthetic Biology!

What is Synthetic Biology?

In my work I write about nanotechnology and synthetic biology and over the next couple of weeks I would like to describe what is happening in these high technology fields. I start with synthetic biology. I am not a scientist and cannot give any form of technical description of how they do what they do. I can present a kind of sketch though of what they are doing and their aims.

The first question then must be what is synthetic biology? Well it is something that can be described as engineering, biology, genetics or nanotechnology, the most common description is that of applying the concept of engineering to biological organisms. But what does that actually mean?

Well, synthetic biology aims to design and engineer biologically based parts, novel devices and systems as well as redesigning existing, natural biological systems. Practitioners use a systems approach, an organism is seen as a whole, or a system, and can therefore be engineered, very much like a machine.

you see, kid's stuff

The system is reduced to biological parts (bioparts) whose function is expressed in terms of input/output characteristics. Once these parts have been described in terms of their function, isolated, standardised and syntheticaly reproduced, they can then be combined to from new organisms, very much in the way that an engineer would build a machine using standard devices built from standard parts. It is just that they are parts of a living organism.

These standard parts are defined by their DNA, and this can be manipulated in order to make the perfect part for the perfect device. Parts of the DNA can be removed and synthetic pieces used to replace them. Create the right part that does the right job, put in it a carrier cell (known as chassis) and Bob’s your Uncle, you can start to construct your organism.

The Biobricks Foundation is a not for profit organization that aims to keep a register of these standard parts, maintaining open access and promoting technical standardization, something that is seen as holding the key to the further development of synthetic biology.

Obviously to do all of the above you require technical expertise, the process requires computational modeling in order to analyze the complexities of biological entities and to predict system performance. You require DNA sequencing in order to describe the genome and then of course DNA synthesis, to re-produce either part of or the entire genome itself.

But what are the potential areas of application for this technology, and what can they actually do now?

One of the main fields is undoubtedly medicine. Drugs can be produced that are more effective or have fewer or even no side effects, as the genomes of their active components can be adjusted and synthesized. An example is the development of a synthetic version of the anti-malarial drug Artermisinin that could be industrially and cheaply mass produced, and in the near future antibiotics could become much more efficient.

Another existing application is water that changes colour when in contact with different polluting agents making them instantly recognizable. Switches already exist that react to certain types of input. An example could be a cell that is part of a person’s body that reacts to the stimulus of a certain chemical that in turn stimulates the production of another. Imagine for example a device that reacts to a chemical produced by a cancerous cell. This input causes a reaction that produces another chemical to counteract this presence. All working naturally using the body’s energy to function.

Other developments involve the energy sector, the production of plants for bio mass that are not as wasteful as those used today and even the development of synthetic aviation fuels.

In other fields a synthetic form of the silk produced by the Golden Orb spider is under development. This is an extremely strong, fine and lightweight material that could lead the way towards new specialist engineering materials.

They are even working on living computer memory, and  this article describes breakthroughs and results in DNA computing.

Well this is nothing but reasonable, my memory lives in my brain and the memory of my ancestors in my DNA, and now they have the technology to read it and even change it, so why not use it in a computer?

I have written several articles on this and other related topics on the Bassetti Foundation website, and as I said I am no scientist, so all comments and criticism invited and accepted.

Online Gamers as Scientists

If you thought that online gamers were just a load of geeks, incapable of socializing with the outside world, and living within the confines of their own in their bedrooms, you might like to have a look this website called Foldit. Foldit is a game, but its aim is to solve puzzles for science, and players have recently made some remarkable inroads into the world of protein modelling. Below is a model of an Amino Acid, and it is this type of thing that gamers manipulate.
An Amino Acid Protein MoleculeThis article that explains the process is in the online journal Nature, Structure and Molecular Biology, and begins with the following statement:

“Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein. Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.”

The fold it game has existed for a couple of years now. Players create protein structures, with the most stable and low energy structures scoring the most points.

The gamers in general are not scientists and they manually manipulate the model from a base form that is provided to them at the start of the operation. They have a variety of tools but the most important thing is that they have better spatial reasoning skills than computers. Computer models had tried to solve the problem cited above for 10 years without success, gamers produced an adequate model that was then refined by scientists in just 3 weeks.

We could draw similarities to citizen science, having seen posts on this blog discussing loaning out some of your computer’s spare hard disk space and memory to solve scientific problems, and the now common use of similar set ups in astronomy.

Just this week the Astronomy and Telescope journal is entitled Citizen Science, and addresses the issue of amateurs classifying high definition photos of far off galaxies. They say that it is the future of astronomic discovery. See my post on The Bassetti Foundation website for a lay explanation.

The gaming process is an interesting innovation though, as it uses skills that may not be particularly associated with science, but reveal themselves to be extremely important.