US, WASHINGTON (ORDO NEWS) — A vaccine in a year or two? Perhaps not so fast: a sad example of HIV.
Anthony Fauci, head of the U.S. Centers for Disease Control and Prevention, recently expressed confidence that the vaccine for the new coronavirus will be 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 might die, and in the face of unfavorable circumstances, millions of people. And then: in Russia they promise to start testing several vaccines against a pathogen at once on June 29, 2020. In China, volunteers of young ages have already begun to experience something that is called the prototype of the future vaccine. Is Fauci too conservative?
Alas, in reality he is rather overly optimistic. Recall: in 1984, after the discovery of HIV, US Secretary of Health Margaret Huxley told reporters:
“We hope to have ready-made vaccines for clinical trials in about a couple of years.”
36 years have passed since then, and the number of deaths from AIDS caused by HIV during this time exceeded 32 million people. And progress with antiretroviral drugs only partially alleviate the problem: in 2018 due to HIV infection are gone from the life of 0.77 million, because poor countries have poor health care and often do not give their full sick therapy. It would seem that the vaccine is more necessary than necessary: vaccinated 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 period expected by the American authorities?
The thing is that creating a vaccine against a new disease is much more difficult than against a well-studied one. HIV has a number of unique features that prevent us from simply dragging our immune system onto it. It turned out to be extremely difficult to understand which of the immune mechanisms could be the key lifesaver in protecting against HIV.
Due to the record fast genetic variation, even higher than that of the flu, the antigenic variability of this virus is very high. Plus, he is able to trigger the mechanisms of oppression and impaired immunity of a healthy person, he knows how to “hunt hunters” – the very immune cells that the vaccine makers are planning to use against him. Another problem: the virus is “purely human,” and immediately reproducing it in animal models proved to be very difficult.
Scientists over the decades have gone through a bunch of treatment approaches, but successes have been modest. Using attenuated, attenuated virus? It turned out that the immunity that it forms is limited by a very narrow circle of specific viral isolates, and that the slightly mutated (he mutates rapidly all the time) HIV overcomes such protection.
For the same reason, it was not possible to create a recombinant vaccine, in addition to making it safe in the case of this virus is quite difficult: some of its variants could cause immune pathologies. The overall result is one: in order to learn how to deal with such a complex and rapidly changing virus, very long basic research is needed.
We emphasize: we are not saying that a vaccine cannot, in principle, 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. Not against the background of such ultra-advanced vaccines, the standard smallpox vaccine looks like a cart next to the Tesla Model 3.
Coronavirus: a very difficult target for any potential vaccine
Unfortunately, we are forced to state that the new coronavirus, apparently, also applies to those for which the vaccine is very, very difficult to create. His closest relative, the SARS virus (the cause of SARS), which attacked our species in 2002-2003, still has no adequate vaccine to this day. What is the reason?
No, not only that the disease was quickly and effectively suppressed by continuous quarantine, as the press sometimes writes. No, it was undoubtedly suppressed … only everyone in the scientific world was well aware that new variants of similar coronaviruses would continue to appear in the future.
And the development of vaccines from SARS was proceeding, although, no doubt, after suppressing the outbreak of this disease, funds for this direction poured less generously than before. However, in those vaccines that gave good results in animals, not the weakest side effects were found. For example, ferrets given one of the vaccines showed serious inflammatory processes in the liver. In some people with chronic diseases, such inflammation in theory can cause death.
Immunity is a very complex machine: its lack of activity against a particular pathogen can lead us to death. However, the excessive activity of cells of the same immune system is able to make them attack completely safe objects, including cells of some human tissues. That is why vaccines are normally first tested in animals and only then in humans.
Such a scheme is also imperfect: a model animal, firstly, may have other side effects from the vaccine, and secondly, it has slightly different immunity. Therefore, it is not always that what immunizes a conditional experimental mouse well will protect us as well. But this, in fact, is the only way to do without very serious problems if there is something 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 animal tests. And then, with the model animal itself there are certain problems.
Say, the Chinese tried to understand whether immunity was generated from SARS-CoV-2, and for this they infected rhesus monkeys. After one cycle of infection secondary to infect macaques failed – like, it shows that at least temporary immunity to the new coronavirus has .
But here’s the nuance: the fact that coronavirus can infect us, and these macaques, does not say at all that our immunity also reacts to it. We do not know which coronaviruses macaques are ill in the wild. It is possible that their ancestors or they themselves 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 suited for developing a vaccine against a new coronavirus. And now we just do not have time.
Antibody-enhancing: arguably the biggest challenge to a new vaccine
One of the most unpleasant features of 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, which is why the composition of the proteins on the surface of the virus envelope can significantly change.
In practice, this can lead to sad consequences. Suppose a person has suffered coronavirus asymptomatically. Then he is vaccinated against coronavirus – but it’s far from the fact that the “vaccine” copy of the same coronavirus that entered his body later will be correctly “recognized” by the immune system. A sharp, enhanced immune response will begin, possibly accompanied by inflammatory processes. In this case, the concentration of antibodies after administration of the vaccine may not have time to reach the safe threshold necessary to neutralize the virus.
In this case, the presence of a person’s immunity to the first type of coronavirus will facilitate the penetration of the second type of coronavirus into the body’s cells. The problem is that an older relative of SARS-CoV2 (SARS itself) shows an antibody-dependent enhancement. And back in 2011, a scientific paper was published at BMC Proceedings , which showed this. Its authors directly say : “Our data raise reasonable 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 antibody-dependent amplification in SARS-CoV … speaks in favor of increased caution when developing a vaccine against it.” So when you read in the press again: “the vaccine against SARS is almost done, just the epidemic is over” – remember this couple of works.
We emphasize: it cannot yet be argued that SARS-CoV2 has the same ability to use antibody-dependent amplification. There is simply no data on it yet in the right quantities: the virus was discovered only three months ago. But if he has such a peculiarity – and this is possible, because he genetically repeats his “elder relative” 80% – then a safe vaccine against the new coronavirus will be quite difficult to do.
Virologist Michael Suponitsky – we want to emphasize right away that for all his merits, the researcher is ambiguous, and he often puts him in – nevertheless, I’m already sure that SARS-CoV2 has an antibody-dependent amplification. Therefore, he is extremely skeptical about the possibility of creating a vaccine against him:
“It is impossible to create a vaccine against coronavirus, since the infectious process caused by it is accompanied by the development of the so-called phenomenon of antibody-dependent increase in infection
Those. antibodies enhance the infectious process caused by coronavirus … But some kind of vaccine will be created, do not hesitate. Big money will be allocated for it. The more panic, the more money. Give the last. The greedy little hands were already shaking, and the technology had already been worked out. There will be a drug that will cause the production of antibodies in mice. It will be introduced to volunteers, the temperature will be measured and they will be declared completely safe. In a month, antibodies will be determined and they will claim to have created the best vaccine in the world. ”
In other words, former military microbiologist and reserve colonel Michael Suponitsky believes that there will be no safe working vaccine.
We would not be so categorical, and that’s why. In addition to the usual “live” vaccines from a weakened pathogen, there are also so-called recombinant vaccines. Reasonably made vaccine of this type will cause not only the production of antibodies in the vaccine, but also the formation of a set of lymphocytes to avoid unpleasant side effects of antibody-dependent amplification. That is why Pavel Volkov, head of the MIPT Laboratory of Genomic Engineering, believes:
“Experts are quite capable of creating a vaccine against coronavirus, which will take into account the presence of … antibody-dependent increase in infection.
Why are some vaccines not so effective in the world today? 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, and in most cases, old, attenuated (live) drugs are used. Nevertheless, we are technologically ready to develop new ones.”
In general, Volkov is closer to the truth: Suponitsky simply focused in many respects on the era when recombinant vaccines were exotic. Another thing is that what is said in the laboratory of genomic engineering at the Moscow Institute of Physics and Technology is still a much less well-groomed path than classical vaccines.
Three paths to the future
The most pessimistic scenario for the development of the vaccine situation, the Suponitsky variant, is very sad. If he turns out to be right, then a safe and effective vaccine will not appear within a reasonable time.
This will mean that the virus can only be stopped by quarantine, and only the strictest, as in China. The option voiced by the not-so-distant British politicians “to get everyone sick” is purely ethically unacceptable: even with a mortality rate of 1% and the epidemic dying out after it covers half of the world’s population, the victims will be too great.
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 do not think that only the elderly will become victims: from a 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 for a long time, and when new waves of a pandemic appear, it will be introduced again. At least in the area of outbreaks. In Russia, the most likely place for new outbreaks is Moscow. Periodic “closing” of the capital will definitely negatively affect both the economy and the general atmosphere in the country: after all, every tenth of its citizens lives here.
In an optimistic scenario, a variant of Volkov, a recombinant vaccine will be created relatively quickly. They will test it on genetically modified (for “rapprochement” with the human body) animals, they will debug it and in the summer they will begin to try it on people. It should be understood: even in the most optimistic scenario, it will not appear before autumn. Recombinant vaccine is not such a well-developed area so that you can confidently promise that everything will work out in it, and even the first time.
A realistic scenario lies somewhere between the two. In it, a safe and effective vaccine against coronavirus will appear, but not by the fall, and not earlier than 2021, when the bulk of the epidemic waves will already sweep the planet. In fact, this option is also quite “evil.” It means that so far we can only hope for the strictness of quarantine, that is, stopping the virus by the Chinese method. After all, there is no reliable medicine to prevent all deaths from a new disease, and it is not a fact that it will even appear.
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The article is written and prepared by our foreign editors from different countries around the world – material edited and published by Ordo News staff in our US newsroom press.