In Russia, for the first time in the world, a vaccine against coronavirus has been registered, but it seems that no one is happy about this. Many people write that it is impossible to release medical products so quickly, because they will not have time to pass all the checks. Others describe it as a "massive human experiment." It is alleged that even before the third phase of clinical trials, "Sputnik-V" will be administered to millions of Russian citizens - in the next month. It is reported that the new vaccine has many adverse reactions, but it allegedly provides few protective antibodies. Each of these theses is incorrect to one degree or another. However, this does not mean that the vaccine necessarily works. Let's try to figure out how things really are.
First, about the facts. They are as follows: the National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya really created a vaccine based on technology that is technologically different from the foundations of all other coronavirus vaccines developed on our planet today. And it is true that it was registered as the first in the world - but not at all in the way most media in Russia and the West write about it.
Let's take a good Western scientific and pop resource, which normally writes very efficiently and with a good understanding of the problem - ArsTechnica. There, right in the headline, they say: "Russia missed clinical trials of a vaccine against Covid-19, plans to vaccinate millions this month." Similar errors can be seen in the publications of the Russian media: there are so many of them that it makes no sense to cite everything here. Alas, this is an erroneous point of view.
Why, in fact, the vaccine was registered
Let's start with the opinion "it is impossible to release medical products so quickly - they, by definition, will not have time to pass all the necessary checks." The fact is that it is based on a misunderstanding of the very process of developing vaccines in the Russian legal field.
In Russia, it is impossible to begin a wide third clinical phase of trials of a new vaccine (that is, involving risk groups) without receiving temporary registration of such a vaccine from the Ministry of Health. Such registration is given after the first and second clinical phases, which show only whether the new vaccine is harmless, whether it poses significant health risks.
The new vaccine has so far gone through only these two phases: that is, it has not yet been tested to see if it helps to avoid contracting the virus. Volunteers were not kept where it was highly likely to happen. They only checked the level of antibodies to coronavirus and a number of other immune parameters.
So, "Sputnik-V" in reality was registered only temporarily (until January 1, 2021) and just for the purpose of conducting the third phase of clinical trials (the first and second have already been completed, the data on them will be published in August). We quote the registration document itself (we apologize in advance for its Kafkian language):
"Conducting post-registration clinical trials, the results of which are the basis for assessing the ratio of the expected benefit to the possible risk of using a medicinal product upon confirmation of its state registration."
Why then was the registration announced - after all, it turns out that the widespread use of the vaccine "for millions" is still impossible? The answer to this question was given quite a long time ago in an interview with Denis Logunov, one of the key developers of Sputnik-V:
"Registration under limited conditions is needed so that people from the risk group could participate in the study - we are not going to protect healthy volunteers with this vaccine."
That is, without such registration, the vaccine can only be given to those whose age and health are such that they do not belong to the risk groups for coronavirus. And to contain volunteers where it is possible to get infected.
The meaning of the recent registration, therefore, was not to "become the first", as they write about it in the press, but in the fact that without temporary registration according to the norms in force in Russia, it is simply impossible to carry out the third phase of clinical trials. The stories about “registering to be the first” come simply from ignorance of how vaccines can be tested in Russia at all.
As we can see, the confirmation of the state registration of the new vaccine is yet to come. And it will happen only after the third phase of clinical trials. Despite this, mass production of the drug is planned from September. How can this be combined with the fact that she is still in clinical trials?
It's pretty simple. First, Roszdravnadzor claims that two thousand people should participate in the third phase of testing over three months. Tens of percent of these people must become infected with the coronavirus in vivo. But this is a theory: vaccinated people will not always face the virus in their daily lives, which means that the third phase may have to be extended. So it's better to have more doses of the vaccine ready.
Second, and more importantly, today the Sputnik-V developers are confident in it to such an extent (like the Ministry of Health) that they consider it necessary to distribute the vaccine to as many people from risk groups as possible, even before the end of the third phase.
It is doubtful that it will be "millions", as they write in the Western press without reference to sources: until October 2020, making millions of doses of the vaccine will be just a production feat. But even tens of thousands of vaccinated people, not to mention several hundred thousand, require the creation of mass production of vaccines. The reasons for the confidence in the safety of its use already during temporary registration - below.
Who will be given the new vaccine and when?
In the meantime, briefly - about risk groups. Among them, no doubt, are doctors. As the epidemic showed, both around the world and in Russia among them the percentage of cases and deaths is higher than in the population as a whole. It is for them that the mass production of the vaccine is mainly calculated since September. It will be accepted voluntarily and - since we are talking about doctors - the most informed part of society about the possibilities of the vaccine.
It is just among them that from the end of August vaccination will begin, which is not included in the third phase of clinical trials. Indeed, this third phase includes only those who are constantly monitored - completely, in all respects, which will be difficult for tens and hundreds of thousands of doctors (and then teachers). It is about them that the head of the Russian Direct Investment Fund Kirill Dmitriev (the fund financed the development and production of the vaccine) says "tens of thousands of volunteers will be vaccinated within a month." Note the difference: not "millions this month", as in the Western press, but tens of thousands over the course of a month - that is, including part of September.
Can this be regarded as a "great experiment on humans"? Is it unethical? It is hard to say. If vaccination is really voluntary (as it is now declared), then certainly not. Typically, experimental vaccination involves not doctors and teachers, but people of all professions. In theory, a doctor should understand better than a regular volunteer what a vaccine is and whether he wants to use it.Teachers, too, must be able to make decisions as well as the general population.
The second most important risk group is the elderly. Today the vaccine is recommended only for people between 18 and 60 years old. This is not because some disadvantages have been identified for older people - this is because the first and second phases of clinical trials were carried out on two groups of 38 people aged from 18 to 60. The reasons for age restrictions are clear: older people are traditionally injected with new vaccines, only by making sure they do not cause health problems in younger people.
In fact, the vaccine has already been administered to people who are over 60. There are many of them among the staff of the Gamaleya Center itself - including its head, Academician Gunzburg (he is under 70). Despite his age, he underwent vaccinations normally. However, this does not mean that it will be administered en masse to elderly people without testing.
Just after August 11, 2020, the so-called "post-marketing phase" of vaccine research began. As noted by the same Gunzburg, one of the tasks in this case is "the study of the possibility of its use in terms of safety and immunogenicity for people over 60 years old, even for 90-year-olds will be investigated." In about three months, if all goes well, Sputnik-V may start to be given to people over 60.
But those who are under the age of 18 do not face it so quickly. According to the law, the third phase of testing on them goes by age groups, and from 8 to 18 there are three such groups. Each of the groups is, in fact, a separate phase within the third phase, and each will take at least three months. This means that for the bulk of children, permission to administer the vaccine will be received only next year. Fortunately, children are the least threatened group.
Oddly enough, but among the first, many foreign citizens will receive the vaccine. The fact is that the UAE, Saudi Arabia, the Philippines, Brazil and a number of other countries have already expressed their desire to participate in the third phase of clinical trials of Sputnik-V.
Why are the developers so confident in the safety of the vaccine? Didn't she give a ton of side effects?
Many media outlets wrote that the vaccine produced many adverse events - either 144 per 38 volunteers, or almost 200 per volunteers. Alas, in the sources (instructions for the use of the vaccine) the picture in figures is slightly different: there were 175 adverse events in 38 volunteers. Of these, 144 passed in 42 days of observation, and 31 did not pass, although in four out of 31 cases the cases were moving towards normalization …
It may seem that more than four adverse events per person vaccinated is a lot. It is alarming that there should be means for anti-shock therapy in places for vaccination. Well-known bloggers generally describe the situation simply: registering such a vaccine is a crime.
Alas, bloggers haven't figured it out a bit. To begin with, about anti-shock therapy: according to the standards of the Ministry of Health, funds for it should be in every room where vaccination is carried out: not only against a new virus, but also any other. Now for the side effects.
To understand whether something is safe or not, it must be compared with analogs, and then also find out what the essence of these very "undesirable phenomena" is. Today, in the third phase of clinical trials, there is another vaccine vaguely similar to the "Hamaley" vaccine - a British vaccine based on a modified chimpanzee adenovirus. Sputnik V uses a modified human adenovirus, but the difference is not that big. How many undesirable phenomena does the British counterpart have, which has not yet received registration?
A related article in the Lancet on Phase I trials of the UK vaccine uses different methods for calculating the incidence of adverse events. But even from them the picture is quite clear: fatigue and headache were typical for most patients.Tens of percent experienced pain at the injection point and general weakness, 60% of those who received the vaccine experienced muscle pain, 61% reported general mild illness, 56% reported chills, 51% fever, 18% of volunteers who did not take antipyretic showed a temperature of at least at 38 ° C, and 2% at 39 ° C and above.
As we can see, in the Russian-speaking segments of social networks they believe in high-quality imported vaccines much more than in Western peer-reviewed scientific journals. According to the Lancet and the developers of the British vaccine themselves, side effects in their recipients are not one in a million, and not one in a thousand - on the contrary, this is the norm. But, just as in the case of the Russian counterpart, in no case were there really serious health consequences - even people with 39 ° C experienced such a temperature for a short time, without any long-term troubles.
It is difficult to directly compare these problems with Russian “adverse events”: the latter also include deviations from the norm that the volunteers do not notice, that is, changes in the results of their blood tests compared to the usual state. In addition, some of the undesirable phenomena recorded from the words of the volunteers, in the British case, apparently, were simply not recorded.
For example, there is not a word about a decrease in appetite (the developers of Sputnik-V mention such a possible consequence). Meanwhile, it is doubtful that the British vaccine is 39 ° C without loss of appetite: at this temperature, it is almost inevitable. Nevertheless, even in spite of different methods of fixing adverse events, their total number in the British and Russian vaccines based on adenovirus is quite close.
Comparing the instructions for using the new vaccine with traditional vaccines is also sobering: there are also many frequent adverse events. And the reason is simple: there is not so much on the planet that cannot cause undesirable phenomena (including even an overdose of drinking water). Vaccines are considered safe not when they do not produce undesirable effects, but when they do not give health hazards for any significant length of time.
Where such confidence?
Well, with undesirable phenomena everything is clear - they are there, and there, and the frequency is comparable. But another question arises. Why are the Gamaleya Center so confident in Sputnik-V that they are already offering doctors vaccinations for them? What allows Gunzburg, the head of the center, to believe that immunity from the vaccine will last two years, since only a few months have passed since the start of testing the novelty?
The thing is that the new Russian vaccine can only be called with some stretch. The very approach of vaccination against diseases using the adenovirus "engine" has been developed at the Gamaleya Center since the 1990s, and more than one vaccine has been made on it.
The latest example of this kind is the Russian Ebola vaccine tested in West Africa. Gamaley adenovirus vaccines against it have been registered for a long time and have passed all three phases of clinical trials. The third phase in Africa was attended by two thousand people, that is, in terms of scope it is the same as planned in Russia for the coronavirus.
The essence of such a vaccine and its differences from foreign analogues are quite simple. In the human body and a number of other animals, the common adenovirus is found, which causes symptoms that we call the “cold” in everyday life. You can take one of the types of such adenoviruses and deprive it of its ability to reproduce in a person (through genetic modification) so that it cannot give the infected person symptoms of the common cold.
At the same time, an insert can be made into the genome of the adenovirus, which will allow the GM virus to introduce into our body a characteristic fragment of another virus - in this case, a new coronavirus. In the case of the Ebola vaccine, the Ebola virus. This is how several years ago a number of vaccines were created at the Gamaleya Center, which have already passed the third stage of clinical trials in Africa (completed in 2019)
The adenoviral approach has one theoretical weakness.It is believed that if a person has been ill with an adenovirus, then his immunity can cope with the adenovirus vaccine so effectively that it simply will not have time to “train” him to fragments of another virus. In the West, this is seen as the main problem with the Chinese adenovirus vaccine CanSino. It uses a type 5 adenovirus, Ad5, as a carrier of a fragment of the coronavirus. 20-50% of the world's population is immune to this virus, which means that it will be more difficult to protect such people with the new Chinese vaccine.
In the Gamaleya Center, the Sputnik-V vaccine uses two types of adenoviral carriers at once: with the first dose of the vaccine, those made on the basis of Ad5 are introduced, and with the second - those based on Ad26. Geographically, these adenoviruses are found in different zones, and a person who has simultaneous immunity against both of these types of viruses is very rare. Actually, tests of such a vaccine against Ebola have shown this: it forms a fairly stable immunity, which, judging by clinical trials in West Africa, lasts two years.
Therefore, Academician Gunzburg, who heads the center, said that the new vaccine against coronavirus can be estimated to work for two years: the delivery person plays an important role in the effectiveness of the vaccine, and in Sputnik-V he is exactly the same as in the earlier two-dose vaccines center named after Gamaleya.
The British vaccine based on adenovirus differs sharply from the Russian and Chinese ones. She uses a chimpanzee adenovirus, ChAdOx1. In theory, this is good: people do not have immunity from it, the body will not have time to "deal" with it before the delivery virus "acquaints" our immune system with the coronavirus.
But the problem is that so far not a single vaccine based on the chimpanzee adenovirus has received registration (in contrast to the Hamaley vaccine). This means that the test cycle for a UK product must be longer if necessary. After all, this is not another product based on a spent carrier made from human adenoviruses, as in Russia or China. Therefore, it can be said with a high degree of certainty that the British vaccine is unlikely to be mass-produced in 2020.
But in the center named after Gamaleya they expect to reach the production of three to five million doses of Sputnik-V per month by the end of 2020. However, we are not quite sure that it will be that easy.
Why it is useful to separate vaccines from politics
The reactions to the vaccine in Russia (and not only) have become politicized, and therefore many react to it according to the principle: since it was done so quickly, it means that they were in a hurry for political reasons, that means it is dangerous.
As we have shown above, this is not the case: the vaccine was registered, first of all, because without temporary registration it simply cannot be fully tested. The fact that, despite this, it will be offered to doctors and teachers is hardly dangerous, because the bulk of the material introduced with the vaccine has long passed clinical trials. Its new component (encoding a coronavirus protein) simply cannot make the vaccine really dangerous for a healthy person.
Are the Russian authorities trying to get political points on the fact of the world's first vaccine registration? Most likely. Just as the US President is trying to get them on false accusations against Chinese health care. Or how they are obtained in China, emphasizing that they were able to cope with quarantine there, from which hundreds of thousands of people died in the West.
But if you are not a politician, then you should separate political games from reality. The reality is that Russia will be able to offer vaccines to certain risk groups before any other country in the world. It is safe to predict that there will be more willing volunteers by the end of the year than Sputnik-Vs themselves.
This is not the result of some wonderful medicine in our country. It's just that the Gamaleya Center was lucky: they had a ready-made vaccine based on the human adenovirus, into which the coronavirus protein was quickly introduced with minimal changes.
China had a similar development, however, based on one (and not two) types of adenoviruses - so it did before us (the Chinese vaccine was ready by the end of July). True, so far his vaccine is approved for use only by the military, but it is unlikely that the matter is in its problems: Rather, everything is explained by the fact that in China, unlike Russia or the West, the coronavirus is practically crushed by quarantine and the issue of vaccination is not so acute that it would be necessary to hurry with it so much.
Maybe it was worth the wait?
The question arises. Is it not in vain that we are in such a hurry? It is clear that clinical trials are needed. But why give the opportunity to vaccinate doctors and teachers? What if they all rush to get vaccinated, and then they have some health problems?
Everyone can answer this question for himself. It is known that hundreds of thousands of people have died from the coronavirus. It is known that not a single vaccine has resulted in even thousands of deaths or long-term damage to health in the last hundred years. This is despite the fact that most mass vaccines were created many decades ago, at a time of much less stringent clinical trial standards.
What is more important to us? The probable possibility of saving tens of thousands of lives or the unlikely risk of harm from a vaccine that can hardly be called new and the bulk of the material of which has long been tested?
Of course, there will always be those who choose not to get vaccinated. But we would advise you to pay attention to one little thing: vaccine developers know much more about them than antivaccinators. However, in the case of the Gamaleya center, they, including the head of the center, have already been vaccinated. Perhaps Academician Gunzburg and Doctor of Biological Sciences Logunov know some details that escaped the attention of commentators and bloggers from social networks? Future will tell.
Will the vaccine be effective?
Above, we showed the reasons why 69-year-old Gunzburg calmly injected himself with the "new" Sputnik-V vaccine: there is not much new in it and that is why it is safe. Her adenovirus "horse" has long gone through all phases of clinical trials in its anti-ebolovirus version. And has shown no severe or long-term side effects. Later, on the same basis, in the same center, a vaccine was made against MERS, a virus related to the new coronavirus.
All that is really new in it is the gene encoding the coronavirus protein. By itself, this protein does not pose a noticeable danger to humans, it is simply physically too small for it to be able to do anything other than “acquaint” our immunity with the coronavirus. In addition, in a short time after vaccination, it disappears from the body and cannot have a long-term effect on it.
But this only means that the new vaccine is harmless. Whether it will also be useful is another question. Unfortunately, there is quite a bit of data here. Yes, our press has already rushed to write that, as it were, the level of antibodies that neutralize coronavirus after the new vaccine is low, only 49, 3.
The problem is, of course, this is not the case. The level of antibodies capable of neutralizing a particular virus and sufficient to protect against it is always different. No one has yet done a massively successful coronavirus vaccination.
Therefore, it is completely unknown whether the level of 49.3 antibodies neutralizing it will be enough to prevent a person from contracting such a virus. To make this clear, a third phase of clinical trials is needed - one in which people will be exposed to the risk of infection, which so far, in the first and second phases of clinical trials, simply did not exist.
It is likely that Sputnik-V should help some of the vaccinated. This is indicated by the fact that antibodies were found in all 100% of the volunteers after the vaccine. Of the vaccines being developed in the world, not everyone succeeds. For example, some of the Chinese do not show it.
But for protection against coronavirus, cellular immunity can also play a significant role, and its parameters after vaccination with a novelty have not yet been published.As a result, it is impossible to say in advance what percentage of those who received the Russian vaccine will not get sick before the end of the third phase of clinical trials, but it has just begun (after registration on August 11, 2020).
Therefore, from a scientific point of view, it is simply too early to predict the success of this particular vaccine. Whether it will protect 15% or 95% of its recipients is not yet known. And it is unlikely that it will be reliably known earlier than November this year. We would not hope so strongly that she will become a panacea for a new disease. As Naked Science wrote back in the spring, there are cases when it has not been possible to create normal vaccines for viral diseases for decades.
But one thing should be understood: there is a demand for the vaccine, and it is very high. In June 2020, the excess mortality in Russia was 25.5 thousand. And although according to Rosstat, only 12 thousand of these people were affected by the coronavirus, there are serious reasons to suspect that the rest of them simply could not be identified. The reason is that after the first days of illness, there may no longer be a coronavirus on a smear from the throat (it has already "gone down"), and it is rather difficult to wash from the bronchi (where it is throughout the entire illness), and such a technique is not suitable for mass testing. good.
Therefore, with some roughness, it can be assumed that in just one June 2020, the coronavirus in Russia killed a quarter of a hundred thousand people. This is a lot: as a result, the overall mortality rate in the country soared by more than 18%. In autumn, conditions for the spread of coronavirus will be much better than June.
As the events of the spring showed, today the Russian state and society are simply not decisive enough to organize quarantine measures of the Chinese or Vietnamese level of effectiveness. Therefore, most likely we will end this year either with a vaccine against the coronavirus, or with a huge number of victims from it. It remains to hope for the first option and prepare for the second.