When will the coronavirus vaccine be made: the good, the bad and the "evil" scenarios

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When will the coronavirus vaccine be made: the good, the bad and the "evil" scenarios
When will the coronavirus vaccine be made: the good, the bad and the "evil" scenarios
Anonim

In Russia, they promise to start testing the vaccine in the middle of summer. In the US, they intend to release it in the middle of next summer, and in China they are already testing it. At the same time, a number of experts claim that it will not be possible to create it at all in the foreseeable future. Why are there such differences of opinion? Will it actually be created, and if so, in what time frame?

Coronavirus on the cell surface

A vaccine in a year or two? Perhaps not so fast: the sad example of HIV

Anthony Fauci, head of the US Centers for Disease Control and Prevention, recently expressed confidence that a vaccine against the new coronavirus will become available to the public 12-18 months after March 2020.

It seems to many that this is somehow very slow, because by that time hundreds of thousands may die, and in an unfavorable combination of circumstances, even millions of people. And then, in Russia they promise to start testing several vaccines against the pathogen at once on June 29, 2020. In China, young volunteers have already begun to test something that is called the prototype of a future vaccine. Is Fauci too conservative?

Alas, in reality he is rather overly optimistic. Recall: in 1984, after the discovery of HIV, US Health Secretary Margaret Huxley told reporters:

"We hope that a vaccine for clinical trials will be ready in about a couple of years."

Since then, 36 years have passed, and the number of deaths from HIV-related AIDS during this time has exceeded 32 million people. Moreover, progress with antiretroviral drugs has only partially mitigated the problem: in 2018, due to HIV infection, 0.77 million died, because poor countries have poor medicine and often do not provide their patients with full-fledged therapy.

It would seem that the vaccine is more needed here: vaccination is almost always much cheaper than treatment, even third world countries can afford it. Why is it still not there, even a third of a century after the date expected by the American authorities?

The point is that it is much more difficult to create a vaccine against a new disease than against an already well-studied one. HIV has a number of unique features that will not allow our immune system to be “trained” on it. It turned out to be extremely difficult to understand which of the immune mechanisms can be the key "magic wand" in protection against HIV. Due to the record fast - even higher than that of influenza - genetic variability and antigenic variability of this virus is very high.

Plus, he is able to launch the mechanisms of suppression and violation of the immune system of a healthy person, he knows how to "hunt for hunters" - the very immune cells that, in theory, the creators of the vaccine are planning to use against him. Another problem: the virus is "purely human", and it turned out to be very difficult to immediately reproduce it in animal models.

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Scientists have gone through a bunch of approaches to treatment over these decades, but the successes have been modest. Using a weakened, attenuated virus? It turned out that the immunity that it forms is limited to a very narrow circle of specific viral isolates, and the slightly mutated (it mutates rapidly all the time) HIV already overcomes such protection.

For the same reason, it was not possible to create a recombinant vaccine, in addition, it is rather difficult to make it safe in the case of this virus: some of its variants could cause immunopathologies.The bottom line is the same: to learn how to deal with such a difficult and rapidly changing virus, very long fundamental research is needed.

Let us emphasize: we are not saying that a vaccine, in principle, cannot be created. For example, by 2015, the same Russian center "Vector" completed the first phase of clinical trials of an HIV vaccine, but there were no further phases yet - they were not given funding. But the problem is that this task is very difficult. Read the work that describes it, or an article about one of its Western counterparts. Against the backdrop of such ultra-advanced vaccines, the standard smallpox vaccine looks like a cart next to a Tesla Model 3.

Coronavirus: a very difficult target for any potential vaccine

Unfortunately, we are forced to state that the new coronavirus, apparently, also belongs to those for which it is very, very difficult to create a vaccine. Its closest relative, the SARS virus (the cause of "atypical pneumonia"), which attacked our species in 2002-2003, does not have any adequate vaccine to this day. What is the reason?

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No, not only that the disease was quickly and effectively suppressed by continuous quarantine, as they sometimes write in the press. No, it was undoubtedly suppressed … only everyone in the scientific world understood perfectly well that new variants of similar coronaviruses would continue to appear in the future.

And the development of vaccines against SARS went on, although, undoubtedly, after the suppression of the outbreak of this disease, funds for this direction poured less generously than before. However, those vaccines that gave good results in animals did not show the mildest side effects. For example, ferrets given one of the vaccines showed severe liver inflammation. In some people with chronic diseases, this inflammation can, in theory, be fatal.

Immunity is a very complex machine: its insufficient activity against this or that pathogen can lead us to death. However, the excessive activity of cells of the same immune system is able to force them to attack completely safe objects, including cells of some human tissues. That is why vaccines are normally tested first on animals and only then on humans.

Such a scheme is also not ideal: the model animal, firstly, may have other side effects from the vaccine, and secondly, it has slightly different immunity. Therefore, not always what immunizes the conditioned experimental mouse well will protect us as well. But this is, in fact, the only way to avoid very serious problems in case something goes wrong with the vaccine.

Unfortunately, for SARS-CoV-2, testing on model animals is rather difficult. Thousands of people per day die from this virus in the world: no one has time to wait for tests on animals. And besides, there are certain problems with the model animal itself.

For example, the Chinese tried to understand whether immunity was produced from SARS-CoV-2 and for this they infected rhesus monkeys with them. After one cycle of infection, it was not possible to infect the macaques a second time - it seems that this shows that there is at least a temporary immunity to the new coronavirus.

But here's a caveat: the fact that the coronavirus can infect both us and these macaques does not at all mean that our immunity reacts to it in the same way. We do not know what kind of coronaviruses macaques get sick in the wild. It is possible that they or their ancestors have already encountered something similar, so their immunity in this regard is different from ours. It takes time to understand exactly which model animal is best for developing a vaccine against the new coronavirus. And now we just do not have time.

Antibody-dependent amplification: possibly the biggest challenge for a new vaccine

One of the most frustrating things about coronaviruses is that many of them have antibody-dependent enhancement.Like some other RNA viruses, during reproduction (self-copying in the host cell), they make many mistakes, due to which the composition of proteins on the surface of the virus envelope can change significantly.

In practice, this can lead to dire consequences. Let's say a person suffered from the coronavirus asymptomatically. Then he is vaccinated against the coronavirus - but it is far from the fact that the "vaccine" copy of the same coronavirus, which entered his body later, will be correctly "recognized" by the immune system. A sharp, enhanced immune response will begin, possibly accompanied by inflammatory processes. At the same time, the concentration of antibodies after the introduction of the vaccine may not have time to reach the safe threshold required to neutralize the virus.

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In this case, a person's immunity to the first type of coronavirus will make it easier for the second type of coronavirus to penetrate the cells of the body. The problem is that the older relative of SARS-CoV2 (SARS itself) shows antibody-dependent enhancement. And back in 2011, a scientific paper came out at BMC Proceedings that showed this. Its authors say bluntly: "Our data raises valid concerns about the use of the SARS-CoV vaccine in humans."

In 2016, the same conclusion was repeated by another group of researchers: "The presence of an antibody-dependent enhancement in SARS-CoV … speaks in favor of increased caution in the development of a vaccine against it." Therefore, when you read again in the press: "The SARS vaccine is almost done, the epidemic is just over," remember this couple of works.

We emphasize that it cannot yet be argued that SARS-CoV2 has the same ability to use antibody-dependent enhancement. There is simply no data on it in the required quantities: the virus was discovered only three months ago. But if he has such a feature - and this is possible, because genetically he repeats 80% of his "older relative" - ​​then it will be quite difficult to make a safe vaccine against the new coronavirus.

Virologist Mikhail Supotnitsky (we immediately want to emphasize that for all his merits, he is an ambiguous researcher, and he is often "brought in"), nevertheless, he is already sure that SARS-CoV2 has an antibody-dependent enhancement. Therefore, he is extremely skeptical about the possibility of creating a vaccine against it:

“It is impossible to create a vaccine against coronavirus, since the infectious process it causes is accompanied by the development of the so-called phenomenon of antibody-dependent intensification of infection.

Those. antibodies enhance the infectious process caused by the coronavirus … But they will create some kind of vaccine, do not hesitate. Big money will be allocated for it. The more panic, the more money. They will give the last. The greedy little hands are already shaking, and the technology has already been worked out. A drug will appear that will cause the production of antibodies in mice. It will be introduced to volunteers, measured temperature and declared complete safety. In a month, antibodies will be determined and declared that they have created the best vaccine in the world."

In other words, former military microbiologist and reserve colonel Mikhail Supotnitsky believes that there will be no safe working vaccine.

We would not be so categorical, and here's why. In addition to the usual "live" vaccines from a weakened pathogen, there are also so-called recombinant vaccines. An intelligently made vaccine of this type will cause the vaccinated person not only to produce antibodies, but also to form a set of lymphocytes, which will avoid the unpleasant side effects of antibody-dependent amplification. That is why Pavel Volkov, head of the MIPT genomic engineering laboratory, believes:

“Experts are quite capable of creating a vaccine against coronavirus, which will take into account the presence … of an antibody-dependent increase in infection.

Why are some vaccines not very effective in the world now? Because there are companies that take into account economic factors and do not want to pay for new R&D.

Therefore, there are still so few modern recombinant drugs, and in most cases old attenuated (live) drugs are used. Nevertheless, technologically we are fully prepared to develop new ones."

On the whole, Volkov is closer to the truth: Supotnitsky was simply largely oriented towards the era when recombinant vaccines were exotic. Another thing is that what they say in the MIPT genomic engineering laboratory is still a much less well-trodden path than classic vaccines.

Three paths to the future

The most pessimistic scenario for the development of the vaccine situation, Supotnitsky's version, is very sad. If he is right, then a safe and effective vaccine will not appear within a reasonable time frame.

This will mean that the virus can only be stopped by quarantine, and only the strictest, as in China. The option, voiced by the narrow-minded British politicians, “get everyone sick” is purely ethically unacceptable: even with a mortality rate of 1% and the epidemic dying out, half of the victims will be too much.

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Billions of people live on the planet, the death of even every two hundredth is more than 35 million corpses, a new world war. And one should not think that only old people will become victims: from the disease, although much less often, people of moderate age also die. Up to a baby in the USA or a 13-year-old in London.

In such a pessimistic scenario, quarantine can be dragged out thoroughly, and when new waves of a pandemic appear, it will be reintroduced. At least in the area of ​​outbreaks. In Russia, the most likely location for new outbreaks is Moscow. The periodic "closure" of the capital will definitely negatively affect both the economy and the general atmosphere in the country: after all, every tenth citizen lives here.

In the optimistic scenario, Volkov's version, the recombinant vaccine will be created relatively quickly. It will be tested on genetically modified (to "get closer" to the human body) animals, debugged and from the summer will begin to try on humans. It should be understood: even in the most optimistic scenario, it will not appear before autumn. The recombinant vaccine is not such a well-developed area to be confidently promising that it will work out right the first time.

The realistic scenario lies somewhere between the two. A safe and effective vaccine against coronavirus will appear in it, but not by autumn, and not earlier than 2021, when the bulk of the waves of the epidemic will already sweep across the planet. In fact, the implementation of such an option means that so far we can only hope for the severity of quarantine: there is still no reliable medicine that prevents all deaths from a new disease, and it is not a fact that it will appear at all.

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