COVID-19 Vaccines, Which Choice?

Two weeks ago, I wrote a post about COVID-19 vaccines, and today I have another! On 15 November the Bassetti Foundation hosted an online event called COVID-19 Vaccines, which choice? I attended, and wanted to propose some of the content for discussion here.

Who to Vaccinate First?

The choice of who to vaccinate is not quite as simple as it looks. The vaccines are a scarce resource, so there is more demand than supply. Choices have to be made about how to use them, clinical but also ethical choices.

Vaccines are a technological fix, which means in this case that they can only work alongside broader measures. We might think that the world is ready for a global vaccination strategy, but there are problems with such an idea. In order to get to a business as normal routine (like last year) the pandemic will have to be under control (or eradicated) everywhere, as travel will spread it once more from zone to zone. One international conference will bring all continents back in contact.

But in the current situation we see competition between blocks and states for the vaccines. The US boast about their developments, the UK are the first, the EU have bought a job lot. This leads to scarcity in other parts of the world, where infrastructure and buying power might not be so great.

Without involving these places though, the plan will fail, as COVID will continue to circulate, put the medical facilities under great strain and kill people. And it will continue to spread back into places where it was under control, through business travel.

Published Strategies

The World Health Organization Sage Values Framework offers an overview of goals, values and then priority groups for a vaccine strategy. It’s free to download here. There are two main aims, to protect the vulnerable and to slow down the spread, but here we need to open a discussion.

It might seem obvious to administer the vaccine to the old and hospital staff first, but this is untested as a strategy. It may save some lives in the short term, but will it slow the spread of the virus? Or better, is it the most efficient way to slow the spread?

The most mobile are those who spread the virus, students, business people, workers who interact with lots of people. Maybe vaccinating these types of people would slow down the spread. Now maybe such a strategy would lead to more deaths in the short term, but if strain on the health system and other social and economic factors were taken into account, over years, the strategy might lead to less deaths.

The slower the spread the better, and the lower the global long term death rate. So this choice is not as obvious as it seems. One side of the plan has to be prioritized, without any data on possible effect. There is little evidence about whether and how the principles and goals support each other, the strategies are based on intuition.

 The European Commission has also published its vaccination strategy for global public good. This strategy (available here) leans more towards the practicalities of aiding the development and distribution of vaccines, its objectives are the following:

  • ensuring the quality, safety and efficacy of vaccines
  • securing timely access to vaccines for Member States and their population while leading the global solidarity effort
  • ensuring equitable and affordable access for all in the EU to an affordable vaccine as early as possible
  • making sure that preparations are made in EU countries regarding the roll-out of safe and effective vaccines, addressing transportation and deployment needs, and identifying priority groups which should gain access to vaccines first 

Below this level the nation states have to implement their own strategy based upon their own interpretations and cultural norms.

Trials and Participation

As vaccines are developed, a further problem arises. Less people are prepared to take the risk of participating in a trial for new vaccines if there is already one available. So the trials are more difficult to run. This problem occurs again later in the strategy, because once the bulk of the population has had the vaccine, those remaining are less likely to want to do it. They feel at less risk, but this means that the virus is never eradicated.

But do we need more vaccines? Yes is the answer. In the last post I mentioned mDNA vaccines, which are better for people with allergies than the current mRNA version. mDNA vaccines only lead to antibodies being produced against the spike protein, while RNA can produce a broader spectrum leading to more alergic reactions.

Another issue is availability. More producers can produce more vaccines, so the supply issue can be better addressed.

A related question is posed by not knowing how long the antibodies will remain strong enough to fight off infection. Immunity is not forever, and if it is only for months (as suggested) then vaccination will have to be repeated. If there are supply problems, we might find ourselves in the position of having to vaccinate the at-risk categories for a second time before those deemed not at risk have received their first dose!

So the more the merrier!

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!

Updates: Working Together Against Corona

Thanks to everyone who sent in suggestions to add to the database of initiatives aimed at helping slow the spread of Corona. I am going to take a look at some of those suggested in the hope of offering you all a little inspiration before you go into the shed to invent something spectacular.

Issinova have designed a valve that can be fitted to an already commercially available Decathlon underwater swimming mask (snorkeling) so that it can be used to provide oxygen from a ventilator machine in sub-intensive care. The company makes the design freely available on its website. See one in the photo above.

Although the solutions are not certified they can be used in case of an emergency situation in which the hospital does not have enough masks for the numbers of patients.

Andrea Tarantino, a stationer from Milan, is using a 3D printer to produce protective masks that are able to defend both himself and other shopkeepers from infection from COVID-19. Using a non-professional 3D printer, he is able to produce a mask starting from a sheet of acetylene in six hours. Not quick, but he is able to supply all of the shopkeepers in the area. See how good your Italian is via the link.

Belgian business ZoraBots is working to make a stock of robots currently stockpiled in their warehouse freely available to help elderly and isolated people connect. They are offering these robots to care homes, and if you have chance, take a look at the link to see what they can do.

Returning to Italy, a crowdfunding is currently running for the Milan Mechanical Ventilators project, promoted by Cristiano Galbiati, Professor at the GSSI (Gran Sasso Science Institute) and Princeton University. The objective is to develop a new (simple and safe) device that conforms to HRME guidelines and is quickly mass producible.

Students at Delft Technical University have produced a prototype of a simple ventilator machine that can be assembled and used in hospitals if other machinery is not available. The prototype is the result of 3 weeks work involving 50 students. The machines are currently being tested, but could be locally produced at a rate of 40 per day. Test your Dutch via the link.

Keep them coming in! All languages accepted. All suggestions to: anticovid19(at)
Replace the (at) with an @