‘About 70 million people can die from COVID-19. It is better to avoid it and receive a vaccine’

An interview with a virologist from the USA. Part One: about COVID-19, the potential of the third Russian vaccine and weak points of Sputnik V

“With the mortality rate we see now (around 1% of all people who had COVID-19 die on average), we can calculate that if all the population of the globe contracts the disease, about 70 million people will die. It is better to avoid it. Vaccination is a reply,” reflects one of the most famous American virologists, Director of the Global Virus Network, an adviser to the World Health Organization, a grandson of Kazan Imperial University’s rector Konstantin Chumakov. In the first part of the interview with Realnoe Vremya, he told us about the potential of the third Russian vaccine against coronavirus, evaluated the danger of new COVID-19 strains and specified Sputnik V’s weak points.

“Mutations of COVID-19 are not a very pleasant development of events

Mr Chumakov, I would like to start the conversation with your evaluation of the danger of new coronavirus strains. Scientists say that the British strain is twice more contagious than the previous forms, while the disease develops worse with a higher mortality rate. How should we fear the arrival of new strains?

Mutations of COVID-19 are, without doubt, not a very pleasant development of events. But at the same time, it is quite expected. When COVID-19 appeared as early as in late 2019, it wasn’t the one that circulated mostly in 2020. The virus mutated last spring already, and this allowed it to spread faster. These mutations affect the spike protein the virus attaches to the cell with. As this coronavirus used to “live” in bats in nature, after switching to humans, it had to adapt, that’s to say, find the most convenient form for this spike so that it suits human cells better. And such adaptation happens gradually: mutations appear. And if they make the virus spread faster, precisely such mutation will be selected. This is what happened last spring.

Now, this virus keeps adapting to human cells, and variants of the virus are appearing that carry various mutations making it more capable of proliferating. Particularly, the British variant had several mutations, a variant appeared in South Africa too. The only thing we know about them is that they proliferate better, that’s to say, the virus spreads faster.

It is unclear yet if these are deadlier. It is hard to answer this question — there isn’t accurate data indicating this. As for the faster spread of the new strains, this is likely to be true because these variants travel from country to country and gradually become dominating and circulating. While old variants will step by step disappear.

Mutations of COVID-19 are, without doubt, not a very pleasant development of events. But at the same time, it is quite expected

“The virus gradually picks a key to the lock of the human cell”

The new virus is thought to adapt to the host — it becomes more contagious but less deadly. It needs this to spread easier. Isn’t this process so obvious in the case of coronavirus? In other words, the new strains are considered to be more contagious and at the same time, as scientists assume, can lead to a bigger number of deaths. Or is the supposed mortality rate higher only because of the active spread of the virus?

There are two different tendencies that are determined by completely different mechanisms of adaptation. Of course, like any living creature, the virus wants to proliferate and live longer. It is Darwin’s law: the one who reproduces better wins the evolution. This is especially noticeable among viruses that have just switched from one host to another. To infect the cell, it is necessary for the virus that a protein on its surface (it is the spike in the case of coronavirus) interact with some protein receptor on the surface of the human cell (it is ACE2 protein in the case of coronavirus). A human and a bat have different proteins. The virus of the bat adapted in evolution, and it has a key to open the mouse’s cage. But this key doesn’t really fit the human cage. This is why the virus picks keys: it tries to open it this and that way. And the mutation creating the best key gets fixed.

It is a natural process of adaptation to life on human cells. This process will end with time when the virus finds the optimal key. And then it will unlikely change — there won’t be an impetus for such a change. But as a result of evolution, the virus will adapt and start to reproduce better than now.

And it is still unknown if this will bring to greater pathogenicity and the capability of causing a severe case of the disease, maybe yes and maybe not. From a strategic perspective, the viruses that won’t cause a severe course of the disease will be selected, of course. It is the rule for all viruses that switch from one host to another. But this won’t happen right away. This process will take much time. This is why one shouldn’t hope one can wait it out. Vaccination is now the only sensible solution. To wait for the virus to weaken... This will happen long-term. But you’d better not count on it.

When will the virus become weaker? Are we talking about decades?

It takes years. Everybody will have the time to contract it over this time. With the mortality rate we see now (around 1% of all people who had COVID-19 die on average), we can calculate that if all the population of the globe contracts the disease, about 70 million people will die. It is better to avoid it. Vaccination is a reply.

This is why one shouldn’t hope one can wait it out. Vaccination is now the only sensible solution. To wait for the virus to weaken... This will happen long-term. But you’d better not count on it

“There is yet no answer if immunity after a vaccine will be effective against the new strain

Do you think the vaccines against COVID-19 that had been created before the appearance of new strains will be able to protect people who were vaccinated from all new mutations?

Nobody can clearly answer this question. It is suspected that the antigen structure (that’s to say, the ability to be recognised by antibodies) of the South African strain altered. But it doesn’t seem that the British strain’s structure did — those antibodies that are generated in human to vaccines and the virus that used to circulate neutralise it quite well. I mean the English variant doesn’t seem to have such a problem. However, some scientific data suggests that a lot of people who had COVID-19 don’t have antibodies that would neutralise the South African strain. This is alarming.

But we are talking about only those who had the only variant of the virus, not those who were vaccinated. So there is yet no answer if immunity after a vaccine will be effective against the new strain. But there will be an answer soon, as active research is underway.

Does it mean that natural immunity won’t be effective against the South African strain, while there is some hope for immunity after a vaccine?

Neither is this clear. Perhaps, immunity to the new variant of the virus won’t be as effective as it is to the old one. Its capability of being neutralised by such antibodies reduced. But it isn’t zero. It is unclear so far what will happen to the antibodies that were produced in reply to a vaccine. But all developers of vaccines perfectly understand this moment. And some companies have already begun preparing a vaccine from the altered variant of the virus.

In other words, even if the fears are confirmed, a vaccine that’s effective against the new strain can be created quite quickly.

Will the mechanism of a vaccine against COVID-19 be similar to the mechanism of a vaccine against the flu? Different flu strains circulate every year, and this is considered when making a vaccine...

The same can probably happen in the situation with coronavirus. The ability to quickly change (antigenic drift) the flu has is quite a rare occurrence among viruses. All other viral vaccines made decades ago against the viruses that circulated in the past century are still effective. The flu is an exception. It is unclear at the moment if coronavirus will follow the pattern of the flu or not. Theoretically, it can. Especially if such an evolution of coronavirus goes on. But it’s early days to discuss this. I personally hope this won’t happen. And some time later coronavirus will adapt and stop there.

It is unclear at the moment if coronavirus will follow the pattern of the flu or not. Theoretically, it can. Especially if such an evolution of coronavirus goes on. But it’s early days to discuss this

“A lot of doctors say they are waiting for precisely the vaccine of the Chumakov Centre to appear”

Have you received a vaccine yourself?

I have, I have received the vaccine by Pfizer. Two vaccines — Pfizer and Moderna — are permitted in the USA at the moment. And their efficiency isб give or takeб identical.

The third Russian vaccine — CoviVac developed by the Chumakov Centre named after your father — is about to be launched. Documents on its authorisation are expected to be obtained in the middle of February. Many fear this vaccine made on the basis of the whole-virion virus. Can you allay the fears and explain how it works?

All three Russian vaccines against coronavirus are based on very different principles. Sputnik V vaccine is an experimental adenoviral vector-based vaccine. The one made in Novosibirsk’s VECTOR — EpiVacCorona — is a peptide vaccine. It is made of chemically synthesised pieces of the protein in the hope that they will cause an immune response. This is also an experimental vaccine — it simply has no equals in the world. If it proves to be effective, it will be the first vaccine of this kind in history. Both vaccines are quite promising. But they are new and made of not really tested technologies.

The Chumakov Centre’s vaccine is made of a completely classical approach. The virus is grown in a bioreactor, then it is cleaned and inactivated, as a rule, by formalin. It is a classical method, a tested technology. There is in general a big number of vaccines based on this principle. This is why many hope that it will turn out to be effective. But you can never know until you try. Data on this vaccine’s safety and efficacy hasn’t been published yet. I hope it is up to scratch. If they are going to register it, it seems good results have been obtained. Everything seems to be normal. As far as I am concerned, they are preparing a petition for authorisation, which means they have what to show to regulatory agencies.

This vaccine in general must be good. I hear a lot of doctors say they are waiting for precisely this vaccine to appear because it is a tried and tested approach. This vaccine contains the whole set of proteins coronavirus has, this is why an immune response will appear not only to one spike but the whole virus. This, of course, is better than one spike. Potentially, this vaccine can be better than the previous two. Yet, one should make sure of this — there is yet no data to confidently talk about this.

Theoretically, its another advantage is that it won’t be so reactogenic because the virus is killed. While quite an active process takes place when Sputnik V adenovirus vaccine is administered. This is good to create a strong immune response, but, on the other hand, this may not be good from a perspective of a stronger reaction.

Unfortunately, there is very little information about the Russian vaccines. There are only press releases and what leaks in the press. While there is very little trustworthy, checked scientific information that has been published. This is why it is almost impossible to judge it. But we will hope everything will be in order.

The Chumakov Centre’s vaccine is made of a completely classical approach. The virus is grown in a bioreactor, then it is cleaned and inactivated, as a rule, by formalin. It is a classical method, a tested technology. There is in general a big number of vaccines based on this principle. This is why many hope that it will turn out to be effective

“mRNA vaccines are clearer than adenovirus vaccines”

What principles are the most popular foreign vaccines developed by Pfizer and AstraZeneca made of? Do they differ from the Russian vaccines developed according to different approaches much?

And it is correct. It is necessary to try different approaches. It is unknown which of them will turn out to be more effective. AstraZeneca vaccine is based on the principle of Sputnik V. But it uses another adenovirus. If Sputnik V contains a human adenovirus, AstraZeneca’s vaccine uses a chimpanzee’s adenovirus so that immunity to a human virus won’t impede the efficacy of the vaccine. Now it is used in England, India and Australia. But it isn’t used in the USA.

Pfizer and Moderna vaccines are created according to the same principles, it is mRNA vaccines, that’s to say, an RNA molecule encodes the spike protein. This RNA is enclosed in lipid droplets — lipid nanoparticles — to easier deliver RNA to the cell and protect it from destruction and thus stabilise RNA so that it won’t break down before penetrating the cell. Consequently, when RNA enters the cell, it starts to synthesise the spike protein, an immune response is produced later. This is a clearer vaccine to a certain degree than the adenovirus vaccine. The adenovirus vaccine also delivers the gen of this spike inside but together with something else, those particles that come from the adenovirus itself. While mRNA vaccines deliver only one gen. This is their advantage. Such a vaccine can be administered as many times as you like, even 50 times. And the previous vaccine won’t impede every new vaccine.

Unlike the same Sputnik V...

Yes, exactly. This reason why Sputnik V is made of two components of two different adenoviruses is that that in reply to the first vaccine you will produce antibodies to its adenovirus. And if you receive it for the second time, the efficacy won’t be so high and there might be effects of immune hyperactivation. To avoid this, adenoviruses alternate in Sputnik V. But if it is necessary to make a new vaccine against the South African strain, this approach will be doubtful because you can’t make the same a hundred times. Immunity will already impede this vaccine from working.

If a vaccine against coronavirus has to be received annually like against the flu, will Sputnik V developers seem to have to use other adenoviruses?

In fact, yes. But, firstly, there is a limited number of adenoviruses that can be used. Of course, they can use a chimpanzee’s adenovirus or find another option. But then they will have to be back to square one, in fact. It will be necessary to conduct the first, second and third phase of clinical trials for every new adenovirus because it is already a completely different virus. If they made sure of the safety of the 26th adenovirus, it is good news. But if, for instance, developers of a vaccine take the 27th adenovirus, everything will have to start again. And if it is an mRNA vaccine, it is once and for all. It will be an approved platform that won’t have to be examined from scratch.

The amenity of such an approach is that if mRNA vaccines are created once, now other vaccines against different viruses can be made in large quantities. While in the case of adenoviruses, this will be done each time again.

AstraZeneca vaccine is based on the principle of Sputnik V. But it uses another adenovirus. If Sputnik V contains a human adenovirus, AstraZeneca’s vaccine uses a chimpanzee’s adenovirus so that immunity to a human virus won’t impede the efficacy of the vaccine

“At the moment, there aren’t enough vaccines for everybody”

How is the vaccination going in the USA?

Unfortunately, there aren’t enough vaccines for everybody around the world. And it is anyway surprising how quickly it became possible to create vaccines against coronavirus, set up their production, check everything out. The situation with the availability of vaccination is also quite tense in many states in the USA. It is hard to receive a vaccine in the state I live. Now doctors, nurses, residents of old people’s homes are vaccinated. Theoretically, people above 65 years can be vaccinated, but there are few vaccines. Many are rushing and looking for a place to get it. The vaccination is not very well-organised. But the campaign is organised better in some states. For instance, in Florida, everything is organised better. According to the mass media, Israel is the leading country in terms of the vaccination pace. Nearly a third of the population has been already vaccinated, though partly because it is a small country.

I hope the vaccination campaign will become more active. Vaccine production is gathering pace every month.

But generally speaking, vaccination is dividing the world into rich countries for whose population vaccines are more available and poor, developing countries that can’t afford to purchase them more...

It is normal and inevitable. It is always better to be rich and healthy than poor and ill. Obviously, coronavirus vaccines aren’t cheap. And a lot of countries simply don’t have such money to provide all their population with costly vaccines. They are waiting for cheaper ones. At the moment, AstraZeneca vaccine is the cheapest — around $4 per dose, while Sputnik costs $10, Pfizer and Moderna do approximately $30. $30 isn’t much for rich countries. But when you multiply 1,5bn Hindus by $30, it will be a big sum.

By Kristina Ivanova