‘COVID-19 is such a foul virus, but many thanks for children’

Professor Anatoly Altstein from the Gamaleya Research Centre on Russian coronavirus vaccines

‘COVID-19 is such a foul virus, but many thanks for children’
Photo: vesti.ru

Russian virologist, Doctor of Medical Sciences, leading researcher of the Gamaleya Research Centre for Epidemiology and Microbiology Anatoly Altstein about three Russian vaccines against COVID-19. Read why we should thank coronavirus for, why the professor distrusts EpiVacCorona, how many Russians, as Altstein thinks, have antibodies (spoiler: about a third), if those who had the disease should receive a vaccine and when in Realnoe Vremya’s interview with the virologist.

“The efficacy of the EpiVacCorona is very doubted

Three Russian vaccines against coronavirus were registered — the Gamaleya Centre’s Sputnik V, Vector’s EpiVacCorona and the Chumakov Centre’s CoviVac. And Russians will soon have choice — which vaccine to choose depending on the age, chronic diseases and other factors. So what’s the principal difference between these vaccines and which one should be preferred?

The question isn’t simple. As for the Sputnik V, it is an adenovirus-based vaccine. The adenoviral vector has been used for different purposes in gene therapy for many years, and this system is fine-tuned. This approach is also used to make vaccines in the 21st century — the result turns out to be quite good. The safety of such a vaccine has been examined well enough.

Of course, there might be some side effects, but like a usual reaction to a jab. This vaccine completed all three phases of clinical trials, which is very important. The results that were published are interim at the moment. Nevertheless, they are quite significant. Obviously, the efficacy is above 90%.

As for the CoviVac vaccine of the Chumakov Centre, it is also traditional. It is an inactivated vaccine, their number is big enough. It is based on a virus that is accumulated in cell culture, purified, inactivated, aluminium hydroxide is added to it, which stimulates an immune response. This kind of vaccine against different viruses has already been made, theoretically, it is the most feasible and simplest vaccine. The first idea when a vaccine needs to be created: let’s grow a virus, then purify, accumulate, kill it and use a vaccine. The Chumakov Centre took this road.

Though this vaccine seems to be the simplest, apparently, its production isn’t so simple. Here it is important that the vaccine accumulate in a sufficient quantity in cell culture. If it accumulates worse than expected, one has to create a bigger amount of this culture, purify and accumulate it more. The Chumakov Centre seems to have coped with these tasks, conducted the first and second phase of trials. In this aspect, there is no doubt in general.

While the third phase is still ahead for them — they haven’t started it yet. The opinion about this vaccine will depend on the results of the third phase, if it is suitable or not.

As for EpiVacCorona, it is completely original. Other laboratories of the world don’t have such a proposal. On the one hand, it is good when there is something original, right?

Photo: nso.ru
As for the EpiVacCorona, it is completely original. Other laboratories of the world don’t have such a proposal

Yes, on the other hand, when it comes to your health, you don’t care about originality...

I agree, this fact makes huge demands on such originality. It is necessary to firmly prove the efficacy of the vaccine. From what we know about it, it likely has few side effects. And in this parameter, it is in first place among the three Russian vaccines. As for its efficacy...

There hasn’t been published any serious data on this. The vaccine was registered on 13 October last year. More than four months have passed, the third phase of trials should have been completed, but where are the results? Neither is it known when the results will be shown and published. Theoretically, the vaccine is so that its efficacy raises big doubts.

Why?

The main immunogenic component of the vaccine, that’s to say, the one that can provide immunity, is the S protein, namely, spike protein. All virologists already know that on the surface coronavirus has spikes made of the trimer, it is three identical proteins that came together and produced this immunogenic protein. Developers synthesise some of its peptides and then “sew” them to their internal viral protein, which is simply a carrier, the so-called nucleocapsid protein. While this vaccine consists of nucleocapsid protein and three peptides that are put on it. It is unclear how this can create a structure that will create immunity against the S protein. Because if you don’t get this in cell culture, in living cells, how will it fold in a way to provide necessary antigenic determinants? This is very difficult to understand.

The authors of the EpiVacCorona claim that their vaccine is a hundred per cent effective. But there is no hundred per cent effective vaccine in general. It means this will be the first one. Moreover, they say that if a vaccinated person is tested with the help of ordinary tests, antibodies aren’t detected. A special testing system is needed, it is created artificially, and antibodies are detected only in this case. But you will inoculate somebody not against an artificial virus but a natural virus. Such a construction theoretically shouldn’t provide neutralising antibodies.

So the efficacy of the EpiVacCorona is very doubted, and serious experimental evidence that would show that this vaccine will work is necessary. The authors haven’t yet bothered themselves about providing such evidence.

The EpiVacCorona has been tested on volunteers here in Tatarstan...

As for the results of such trials, it was claimed that summaries would be made on the basis of 3,000 volunteers. This also raises big doubts. 3,000 is a very small number. Vaccines are usually tested on 20,000-40,000 people. The Sputnik V vaccine was to be tested on 40,000 volunteers, but it became possible to test it and register the results on around 20,000 people. It isn’t so simple to organise a third phase of trials: to select and persuade volunteers, promise them something, inoculate them and so on. Moreover, some of the volunteers receive a placebo. It is very important to know how big the placebo group was to determine if the vaccine works. If the placebo group is small, you won’t obtain a serious result.

If EpiVacCorona developers plan to vaccinate only 3,000 volunteers, how many people can they inoculate with a placebo? As many as a thousand people. And what can they learn from these numbers? So to be honest, I really doubt it.

Photo: nso.ru
So the efficacy of the EpiVacCorona is very doubted, and serious experimental evidence that would show that this vaccine will work is necessary

“We will have to work to change the adenovirus membrane of the Sputnik V”

If we have to receive a vaccine against coronavirus regularly like against the flu, can the Sputnik V be used again considering that it is based on an adenoviral vector? While the number of adenoviruses is limited...

It is a tough question. It seems we will have to work to change this adenovirus membrane. The number of adenoviruses is big enough, and the task of picking other adenoviruses with the same membrane, the same added coronavirus gen is solvable. I don’t yet understand if this task will be performed.

Now it is known that the Gamaleya Centre is making an arrangement with AstraZeneca, which has its own adenovius-based vaccine. In late 2020, the Russian Direct Investment Fund, the Gamaleya Centre and R-Pharm and AstraZeneca pharmaceutical companies signed an agreement to develop and conduct clinical trials of a combination of coronavirus vaccines.

The sides agreed to develop relationships in business and research within which they will consider the possibilities of joint use of the Russian vaccine Sputnik V and AstraZeneca’s AZD1222 (Editor’s Note: developed for a more persistent and longer protection of people against coronavirus).

The Gamaleya Institute uses two different types of adenovirus for its Sputnik V vaccine — Ad26 and Ad5. As they are different, there isn’t a big problem here. A person is vaccinated with Ad26 first, he has antibodies against Ad26. And Ad5 is used in the second dose. It is a more or less favourable situation. As for AstraZeneca, they use one type of adenovirus and apply it twice. I think will, of course, lower the efficacy of their vaccine because antibodies to the adenovirus will not only completely suppress the immune response, they can even reduce it. As for the US Johnson & Johnson vaccine, the developers took a simple road. They used Ad26 for just one-jab vaccination. The Gamaleya Institute will likely follow the same path in addition to the Sputnik V, such a vaccine will be named Sputnik Light.

Photo: Maksim Platonov
Nevertheless, if during the pandemic a vaccine provides at least 50% protection, it is already not bad. While the Sputnik Light can provide 60-80% protection. It isn’t a bad optionPerhaps, there might be attempts of vaccinating children with the Sputnik Light”

Does it mean that the Sputnik Light vaccination includes one type of adenovirus?

Yes, one adenovirus and one jab. This, of course, will decrease immunogenic activity. Nevertheless, if during the pandemic a vaccine provides at least 50% protection, it is already not bad. While the Sputnik Light can provide 60-80% protection. It isn’t a bad option. Moreover, such a vaccine will be much cheaper. And the inoculation with the Sputnik Light vaccine, which will be administered once, will be easier to conduct.

Virology in general has an urgent problem when a person has to be vaccinated two, three, sometimes four times. It is a complex problem. Some people who received the first vaccine disappear and don’t show up anymore.

Who will be anyway recommended to receive the Sputnik Light? Those who already had the disease and have some antibodies?

The vaccine Sputnik Light will be prescribed for everybody who is prescribed the ordinary Sputnik V. Of course, the Sputnik Light will be less reactogenic. Perhaps, there might be attempts of vaccinating children with the Sputnik Light. In general I don’t think children can have problems with such vaccination against coronavirus. This simply hasn’t been studied yet.

Do you think the vaccination of children against COVID-19 is justified?

It is necessary in order to make sure the majority has antibodies to coronavirus. Such a decision will complicate the spread of COVID-19 among humans.

So we are talking about the renowned herd immunity...

Yes, we are. There is no point in simply vaccinating children against coronavirus because COVID-19 cases among children are mild, some don’t have the disease at all. COVID-19 is such a foul virus, but many thanks for children. The worst thing is when children suffer. In this case, thank God we don’t have it. However, the elderly have severe cases. And the USA recently crossed the tragic threshold: the number of Americans who died from COVID-19 exceeded 500,000 people. These numbers outstrip the total losses of America in three wars of the 20th century, the Vietnamese and the two World Wars.

Do you consider any other Russian vaccines besides the Sputnik have potential to be used for children? Or is the bet on the Sputnik Light?

This issue should be examined separately. The Chumakov Centre’s vaccine could also suit. But it takes big production capacities to make a sufficient quantity of the vaccine. Generally speaking, all these tasks are solvable. When a vaccine is developed, it is possible to expand production capacity and produce it as much as possible, though it isn’t simple.

Photo: Alexander Korolkov/rg.ru
COVID-19 is such a foul virus, but many thanks for children. The worst thing is when children suffer. In this case, thank God we don’t have it. However, the elderly have severe cases

“It is nearly impossible to get 70% of vaccinated people in Russia

Some people are in the risk group, they aren’t recommended to receive the same Sputnik V vaccine, for instance, patients with cancer. What should they do?

The EpiVacCorona could be used for them if its efficacy is proved, though this hasn’t been done yet. And I really doubt that it will be done.

As for those categories that have contraindications to vaccination, the vaccine is not only a means of individual protection of a person who was vaccinated. It is anti-epidemic protection. You will never vaccinate a hundred per cent of the necessary contingent. The country should try to vaccinate as many people as possible, but a hundred per cent is an impossible task. In any case, some people who aren’t recommended vaccination won’t be immunised. The immunity a lot of people have will protect them, and the virus will simply do nothing.

Is the indicator of 70% of the population with antibodies enough for herd immunity?

Enough, of course. But it is nearly impossible to get 70% of vaccinated people in Russia. Once Vladimir Lenin achieved it in the vaccination against smallpox. But it is a more horrifying infection than coronavirus. He achieved such an indicator by making the vaccine mandatory. Children were vaccinated too, moreover, their parents were not asked for permission at times.

Does the 70% include both people who had the disease and those who were vaccinated?

Yes, according to official data, those who were confirmed to have COVID-19 account for around 3% of the population in Russia. However, the virus spread much more, in fact, I think the percentage is even 30%.

When Russia’s consumer rights protection watchdog did research on herd immunity, the third stage showed that even in Tatarstan more than half of the population had antibodies to coronavirus...

It is good. But it would be more sensible to measure neutralising antibodies in these people because it is good have simply S protein antibodies, but they aren’t neutralising antibodies. The latter, unfortunately, are quite hard to be counted in a big number of people. It is a more expensive procedure.

Neutralising antibodies are those antibodies that bind the virus, it stops to work, infect and destroy the cells. This test is done with the help of cell cultures, which, of course, is more complicated and expensive. The ordinary test for antibodies is a serology test, which is much simpler.

Photo: Maksim Platonov
In any case, some people who aren’t recommended vaccination won’t be immunised. The immunity a lot of people have will protect them, and the virus will simply do nothing

“The vaccines will protect from the new strains too”

Do you think that the Russian vaccines will be effective against new strains, particularly the British, South African ones?

At this moment we can think that they will be quite effective against the British and Brazilian strains. The differences aren’t significant. As for the South African strain, it needs to be examined, of course. But scientists working with the American vaccines Pfizer and Moderna think their vaccines protect from the South African strain too. Then the Sputnik should protect too. I am convinced that it will protect from the South African strain too, though perhaps less.

It was claimed that immunity should last for two years after vaccination with the Sputnik...

This claim is based on theoretical prerequisites. Perhaps, this is true. But in practice, we can’t see it yet because the mass vaccination kicked off not a long time ago.

“People who got infected more than six months ago can easily be vaccinated”

If a person had a severe case of coronavirus, which was more than six months ago, should he receive a vaccine? In this case, the Ministry of Health Care of Tatarstan recommends receiving a vaccine and doesn’t require a test for antibodies... Should people who had the disease do a test for antibodies anyway, which isn’t covered by insurance?

I think such people easily can be vaccinated without a test for antibodies. I don’t see such a threat. Even if a person has antibodies and receives a vaccine, there should be no problem.

Shouldn’t there by a hyperimmune response even though there are antibodies?

No, in this case, there shouldn’t be anything pathological.

Photo: Maksim Platonov
I think people who receive a vaccine. If they have some doubts due to their health, they should consult their doctor and receive a vaccine depending on doctors’ decision

Do you assume that coronavirus vaccines will become seasonal like those against the flu?

If this is possible. The fact that the Sputnik is based on an adenoviral vector, on the one hand, allows producing a sufficient amount of such a vaccine. On the other hand, if this adenoviral vector is administered constantly, it will start to impede an immune response. It is a task that has still to be performed. As for RNA vaccines, there shouldn’t be such a problem.

Why do people have different reactions to the vaccination? If I have a look at my acquaintances who have received the Sputnik, it feels like the youth had stronger reactions to the jab, they had a temperature, pain at the injection site, whereas the elderly almost didn’t have any reaction?

All people are different. Not only the age is the case, the state of the nervous system, immunity and so on are considered. So people will have different reactions to the vaccine.

Could you give a tip to people who are considering if they should receive a vaccine against COVID-19? And which vaccine should they receive if they can make choice?

I think people who receive a vaccine. If they have some doubts due to their health, they should consult their doctor and receive a vaccine depending on doctors’ decision.

Now we have a chance of receiving only one vaccine, Sputnik V. As for the other two vaccines, of course, one can receive them, but they haven’t completed the necessary trials so far. And among the two vaccines that haven’t completed the trials, I would trust the Chumakov Centre’s vaccine. As for the EpiVacCorona, we need good evidence it works.

By Kristina Ivanova