Life without a mask and gloves
How to create a vaccine against the virus?
Yuri Zhigalkin, Radio Liberty
How far is it to a coronavirus vaccine? Is the new coronavirus a particularly difficult opponent for the creators of the vaccine? Is the weakening of the self-isolation regime fraught with a sharp outbreak of the pandemic? Should Americans prepare for life in a mask?
We are talking about the prospects of fighting and living with the new coronavirus with Professor Emeritus of Boston University biophysicist Maxim Frank-Kamenetsky.
On May 18, the shares of the Boston biopharmaceutical firm Moderna soared by almost thirty percent, along with the main stock indexes on Wall Street soared. The company announced the encouraging results of the first stage of preliminary testing of its coronavirus vaccine on volunteers. It was a collective sigh of relief. For the first time, there was confirmation that hopes for the creation of a life-saving vaccine are not illusory. The shares of the company, which does not have a single original drug in its portfolio, have increased by three hundred percent since the beginning of the year. The press release caused euphoria among investors who were waiting for good news. The next day, it was replaced by despondency, because upon closer examination, the complete absence of data in this document confirming the initial, even very preliminary, success caught the eye of medical professionals.
Ten days later, the shares of Moderna lost 30 percent of their value. Since then, several prominent experts, including Anthony Fauci, head of the National Institute of Allergies and Infectious Diseases, while maintaining an optimistic tone, warned that the imminent appearance of a vaccine is unlikely to be expected. Their range of forecasts is from six months to one and a half years. That is, the world will most likely have to coexist with a dangerous virus for quite a long time.
– Professor Frank-Kamenetsky, how can we explain what is happening with the Moderna vaccine and to what extent does this success or failure reflect the progress of work on the creation of a vaccine against the new coronavirus?
– In general, from the very beginning it was a very bold project, extremely bold, – says Maxim Frank-Kamenetsky. – Let me remind you that the technology of "Modernity" is that an mRNA molecule is used as a vaccine. This mRNA in the Moderns project is embedded in ribosomal nanoparticles, and a solution of these particles is used as a vaccine. mRNA penetrates into the cell with the help of these nanoparticles, in the cytoplasm of the cell, RNA is read by the ribosome as a protein, this protein is already an antigen that has appeared in the body, it causes an immune response. This is a very beautiful idea that has never been brought to a vaccine that has been tested and used in humans. This is an extremely risky project because it is being done for the first time.
– And if we assume that the shares of the company "Moderna" have been falling sharply for several days, the success of this vaccine is not guaranteed at all? In general, it is clear what she managed to achieve, because at first it seemed that she had succeeded in preliminary trials of her vaccine on humans?
– On the one hand, there were great hopes, and they remain, as in relation to everything that is very high-tech and very modern, not without reason "Modern". On the other hand, skepticism is justified, because it may well not work. They released a press release in which they talked about some preliminary test data with 45 volunteers, they said that these data were extremely encouraging, but they did not give any real data. That is, they said they had such data, but they did not provide it. By professional standards, the publication should be in the form of an article, at least a manuscript of an article that could be read, see the data, see all the figures that give reason for this optimism. It is too early to talk seriously about any results, because they have not led to any results. When the entire blogosphere became full of doubts, their shares plummeted. At first they jumped terribly. Now it is a huge company, it has a huge capitalization. At the maximum, when the stock price jumped after this press release, it was $ 29 billion. For a technology company that has not yet earned a single cent on its product, this is an absolutely unthinkable capitalization.
– This stock movement is very similar to a burst market bubble, especially since there is information that four company executives earned more than $ 20 million by selling part of the shares immediately after the press release appeared. They say it was a pre-planned sale, but skeptics say they timed the release of the press release by that date.
– I do not know how much of a bubble it is, we will see. She is the number one vaccine that the United States administration puts on.
– And if I'm not mistaken, one of the employees of Moderna recently took a high post in the Trump administration?
– The post he took is the head of the committee that decides which of the vaccines to support with big dollars from the government. He did not work in this company, in another, but he was on the board of directors of Moderna.
– We have been living with the virus for about six months, and there is no complete clarity about what it is, at least for the average person. Someone continues to insist that this is only a more virulent version of the flu, but at the same time, data on high mortality from COVID are being brought down on us every day. What can be reliably said about this virus today?
– It has a number of unusual features. Firstly, it is an absolutely perfect virus as a source of a pandemic. In order to create a pandemic, a virus should not be very harmful, that is, it should not cause death with a high probability. Because if the virus kills the first person it jumps over, that person won't have time to pass it on to anyone. The virus should not kill very quickly, that is, there should be a long incubation period. During this incubation period, it is desirable for the virus that it does not manifest itself in any way, so that patients are without symptoms, but at the same time that they are contagious. In the case of coronavirus, somewhere around two weeks, a person may not show symptoms at all and at the same time be contagious. And then the virus can kill someone, not kill someone – it's not so important. This virus is also very interesting in this sense, for some reason, for completely unknown reasons, it kills only old people. Just yesterday, in our state where I live, in Massachusetts, data was released: approximately 6.5 thousand people died from coronavirus, the average age of these people who died was 82 years. That is, he mows down the elderly with some extraordinary selectivity. Children in general practically do not die, young people sometimes die, but very rarely.
– You are talking about high mortality among the elderly, but now the American press has accusations against several governors, including New York Governor Andrew Cuomo, who forced nursing homes to accept infected people who turned out to be carriers of infection and caused widespread infection of several large nursing homes. By the way, in several dozen states, more than half of those who died from COVID lived in nursing homes. Is this factor likely to have had a strong impact on the overall mortality statistics?
– The factor is very important. Why is such a high age of the average deceased associated with the fact that it was rampant in nursing homes? Because he is very contagious, he has a long incubation period, and this has created ideal conditions for his penetration into these homes. It is clear that even before the real alarm was raised, he entered New York through Europe, and not through China. When the flights from China were closed, it had been raging in New York for a long time, just no one knew about it yet, because people had not yet begun to die. By the time they began to die, it had already penetrated almost all nursing homes for a long time, it is easy for it to spread there, because there is very close contact between those who care for and those infirm people who are there. Of course, they are in rather cramped conditions. Throughout the civilized world, in Europe and in America, a significant part of the victims were in nursing homes. Even in Sweden, where no special measures were taken, a huge number of people died there in nursing homes.
– If we go back to comparing COVID with the usual flu? How much more dangerous is he?
– He has a generally higher lethality. Mostly old people die. But if we talk regardless of age, the mortality rate is apparently 10 times higher than that of the influenza virus.
"And that's what makes him particularly dangerous?"
– Yes, it gives him a special danger. And the danger is that what happened in New York almost happened when the health care system almost collapsed. She held out, but she was already on the verge. She survived only because she was quarantined. If they had delayed the introduction of quarantine, it would most likely have collapsed.
– Now the world is living in anticipation of a vaccine, which increasingly looks like the only way to return to normal life without masks and shying away from each other. Do these features of the coronavirus present particular difficulties for creating a vaccine? Is it more difficult to cope with it than with ordinary respiratory infections?
– The search for a vaccine is always the same – we have to reduce the immune response against some protein of your virus. In this sense, there is nothing special about it. In fact, it is easier to develop a vaccine for the coronavirus than for the flu virus. Here's why: the coronavirus contains one RNA molecule, it's long, it's unusually long for respiratory viruses, but it's one molecule. In influenza, the genome consists of several molecules, several chromosomes. Different strains of flu appear all the time, because these RNA molecules combine in different ways. Then it is impossible to develop a vaccine once and for all. Next season, a new composition of RNA molecules is obtained, the old vaccine no longer works. In the case of coronavirus, there seems to be no such danger. The foundation of the coronavirus that the vaccine should hit is the structure of its C-protein. Everyone remembers his image – a ball with spikes. These spikes, each spike is a protein, it's one protein molecule, it's called a C-protein. Through this thorn, it penetrates into the cell. This spike binds to a special receptor on the cell surface, through this binding the virus enters the cell. This is his way of entering the cage without asking. This is his main property, thanks to which he became what he became, before that he was one of the many bat viruses and did not touch a person. When some mutations occurred in this spike protein so that these spikes began to recognize the receptors of human cells, he turned into the worst enemy of the human race.
– Do I understand correctly that the goal of the creators of the vaccine is to build a weakened version of the virus, when faced with which the body will learn to reflect a real full-fledged coronavirus?
– The principle is the same: to provide the body with an antigen, a protein that causes an immune reaction in the body. An antigen that, if a real virus comes, will be perceived by our immune system as if the same antigen has appeared again, it will attack it, antibodies will attack this virus and begin to destroy it, cells will begin to kill those cells that the virus has infected. We have two lines of defense against the invading bandit – these are antibodies and T-cells, the so-called T-killers. These are two lines of defense, they are already ready for battle if you have vaccinated this organism.
– Is there a variant of the natural extinction of the pandemic? At first, it was assumed that this could happen over time, as happens with seasonal flu epidemics?
– In order to achieve this, it is necessary to create a so-called herd immunity, also called "collective" more mildly. What is herd immunity? This is when in your population, whether it is a country or the whole planet, 60 to 80 percent of the population have acquired immunity in one way or another. Either they got sick and their immunity arose, or if the vaccine was made, then they were vaccinated. In general, both should give such numbers of people who have acquired immunity, then the pandemic fades by itself. Since so far the proportion of people who have been ill is much lower all over the world, and in America in particular, in any other country, now there can be no question that the pandemic will end by itself. We put it out, the same Governor Cuomo brags about it all the time, we managed to put it out thanks to quarantine.
– What is the problem with creating a COVID vaccine, or are there no special problems?
– There are no special problems. There are no special problems, except that never in history have vaccines been created within the time frame that we want now. Now two methods have come to the forefront, they are both very advanced, so advanced that the first phase of clinical trials has already been conducted. In order to start using the vaccine, you need not only to make it, you also need to go through two very expensive and difficult tests. The first is to test it on a huge number of people, thousands, even tens of thousands of people. Because it is necessary that it be effective and that there are no significant negative effects. There are two vaccines that have passed the first stage – this is the vaccine we talked about, based on mRNA, the Modern vaccine, and the second vaccine is the one developed at the Jenner Institute in Oxford under the leadership of Sarah Gilbert, this vaccine is based on the use of a virus. If the listeners remember what we talked about when we talked about the mRNA vaccine, we said that the RNA is encapsulated in a nanoparticle, these particles are used as a carrier of this RNA from the outside into the cell. The Jenner Institute takes a different approach. The Oxford group's vaccine uses a virus for this purpose, an adenovirus is a terribly common cold virus, it carries inside its viral particle not RNA, like a coronavirus and like a flu virus, but DNA. This adenovirus, at first it is made harmless so that, God forbid, it does not infect, but even if it infects, the adenovirus is a trifling virus, it just causes an innocent cold. But, nevertheless, it is modified so that it cannot reproduce, but retains the ability to penetrate the cell. And the coronavirus C-protein gene is embedded in his DNA. The end result is the same as that of the Moderna vaccine. A protein inherent in the coronavirus arises inside the cell, and it serves as the antigen to which the immune system of the subject begins to react. This is how immunity against C-protein arises. This is the second way, it is more traditional, it has been done many times in the application to vaccines, to use another virus so that this other virus, with the help of genetic engineering, eventually produces the most important protein of the virus against which you want to get an immune response.
– Well, two groups are leading the competition for the creation of a vaccine. Is it clear when the vaccine may appear? Some prominent professionals urge not to delude yourself on this score, talking about almost a year and a half that may be required for this.
– This is what is being done at Oxford and is being done very successfully, they have passed the first phase of clinical trials, now they have moved on to the next. They promise to complete clinical trials by the end of August. This is a colossal speed, an unthinkable speed for clinical trials of a vaccine. They promise to do it, to test it on tens of thousands of people of different ages, different ethnic groups, and so on. The next obstacle is that you have to accumulate billions of doses of the vaccine to start vaccinating the population around the planet. To acquire herd immunity, it is necessary that 80, some even estimate 90 percent of the population with such a contagiousness as that of the coronavirus, be immunized. This is the second colossal problem, it's just the creation of factories for the production of these vaccines. If this is done consistently, then it all goes far into 2021. In order to do all this within 2020, we need to do it in parallel. Now the work on the vaccine and the creation of production facilities for its manufacture is going on in parallel, at least for these two vaccines that we are talking about. Behind Jenner's group is the giant British-Swedish pharmaceutical company AstraZeneca. I read in reliable sources that Oxford promises to complete the tests by the end of August, and AstraZeneca promises to produce 400 million doses in October. In total, they intend to produce one billion.
– Professor, you are talking with conviction about the relatively imminent appearance of a vaccine, because there is an unprecedented incentive for its creation and there are practically unlimited funds for this, but there are examples of major failures, take at least a vaccine against HIV infection. Is there a high probability that a vaccine against this virus will not be created?
– Of course, in addition to huge successes, there are, as always in science, and many examples of failures, there is no science without this. But evaluating single events in terms of probability is a pretty pointless exercise. To say that this cannot be, that this cannot be done, is easy to say, because it is the easiest thing to say, because it has never happened before that a vaccine for a new virus was made at such a time, even close to these deadlines. There has never been such a pandemic. There was a pandemic, as you know, "Spanish flu", it killed more people than the coronavirus has killed so far. But it was a completely different disease, it was the flu. Half a million people died in America at that time, and there were only a hundred million people in America at that time. But then no one thought about making a vaccine during the pandemic. Just think about the fact that the virus was sitting in China, was just about to fly all over the planet from China, and the sequence of its RNA was already determined, was already available to everyone. Of course, we are now disproportionately more armed than ever before in order for the creation of a vaccine to be crowned with success. But still, of course, there are no guarantees.
– Then a more substantive question. Many countries are now trying to resume a more or less normal life, the work of many firms is resuming, borders are opening in some places. What is this fraught with? Is a new outbreak of the pandemic and mortality likely?
– The virus is extremely contagious. As soon as you begin to increase the interaction between people, there is immediately a danger of an outbreak, and outbreaks will inevitably occur. Any absolutely epidemiologist will tell you that. As long as herd immunity is not ensured, as long as up to 80 or 90 percent of the population does not acquire immunity to the virus, outbreaks will occur and there will always be a danger of a large outbreak, such as the one that occurred in New York, and the type that is now happening in Brazil, such, which occurred in northern Italy, and one that occurred in the UK.
– If the danger you are talking about now is real, then won't those who say that total quarantine and isolation is not the best way to fight infection be right? Society could acquire herd immunity naturally, as it happens in the case of various epidemics. As far as I understand, Sweden has gone this way. And now the virus is simply driven into a corner at an incredible price and at any moment it can jump out of there before the vaccine appears and arrange another massacre.
– The Swedes conducted such an experiment, absolutely correctly, but it is not over yet, they are still far from herd immunity. Because they really weren't so merciless, they still severely limited contacts between people, not all their children go to school, their universities don't work, elderly people don't leave home, and so on. Therefore, they develop herd immunity, but rather gradually. Brazil is a more striking example, because practically no measures have been taken there at all, and the healthcare system there, apparently, as far as I can judge from press reports, is collapsing. It's already a disaster in Sao Paulo. It almost happened in New York. After all, in New York, literally at the last moment, it was possible to extinguish this rapid increase in the number of cases, not to overload the healthcare system. This question has been discussed a thousand times everywhere for a long time: yes, let the old people die, God be with them, young people are almost not sick. The problem is that before all the old people who are destined to die in this way, according to such a rigid approach, all the beds in hospitals will be filled with these dying infected with coronavirus, and then everyone else will start dying: someone will have a heart attack, someone a stroke, someone appendicitis, someone has kidney stones, these people will also die, because there will simply be no beds for them.
– If I'm not mistaken, Sweden recognized that it was necessary to do more to protect older people. What if they had taken special precautions against the older generation?
– It can be done in China, it can be done in a totalitarian state, but you can't do it in a democratic country. To tell everyone under the age of 65 – work, live as you should, as always, and those who are over 65, all go home, if they leave home, they are put in jail. In a democratic country, such approaches do not work.
– In other words, we have a long-term prospect of living in masks?
– As long as there is no vaccine, this will continue. Because it will take a very long time to achieve herd immunity by natural infection in order for so many people to get sick. We have weakened, we will further weaken the rules – outbreaks will begin, it is completely unclear how to deal with the problem of schools, universities, no one can figure out how to do it correctly. When there is a vaccine, everything will be very simple in the United States, in my opinion. Those categories of people who are most vulnerable, they will be vaccinated, these people will not get sick, and those who are not vaccinated, yes, they will get sick, but most of them will not even notice how it happened to them, gradually everything will be fine.
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