Coronavirus, immunity and vaccines
Will the vaccine be the golden key in defeating COVID-19: the most complete and detailed review
The vaccine is considered the only means for the final victory over COVID-19, in its absence , no return to normal life of the pre-quarantine level is expected. Finding an effective vaccine is an urgent public health priority. If enough people become immune to the coronavirus , the infection will not be able to be transmitted effectively. The risk of getting sick will be minimal, and restrictive measures (such as social distancing) can finally be canceled. Mass vaccination is the most reliable way to achieve this result and stop the pandemic. The task of any vaccination is to introduce the body to the causative agent of a particular infection and develop a specific immunity. In this case, the vaccine should make a person immune to COVID-19 infection.
More than 80 companies around the world are striving to create a vaccine against COVID-19 in record time. The suddenly appeared new coronavirus SARS-CoV-2 is deciphered by both scientists and doctors directly "from the wheels".
However, it is not enough to develop the drug itself. It is necessary to make sure that the vaccine not only provides reliable immunity, but is also safe to use. That is, it does not give side effects and is equally well suited for the vast majority of people – including the elderly and those with health problems.
Exactly the same problem is on a global scale. The world's population is about 7.4 billion, and almost everyone will need to be vaccinated. But only about 5 billion doses of all vaccines are produced annually in the world, taken together, about 1.5 billion of them are against seasonal influenza.
The uniqueness and mystery of COVID-19 lies in many phenomena that are absent in other infections to which humanity has already adapted. It is unclear why there is such a big difference in the level of morbidity and mortality in different countries. Why do children practically not get sick, while, for example, the flu is most severe in children. Why do immunosuppressants and corticosteroids help a number of patients with COVID-19 in severe conditions, while immunostimulants save others? While there is no vaccine, doctors are trying to find effective medicines among the well-known drugs used in the treatment of malaria, HIV/AIDS and other immunodeficiency conditions, rheumatism and other autoimmune diseases and viral infections of other etiology.
Immunity – friend or foe with COVID-19
The immune system helps protect us from pathogens such as bacteria or viruses when they enter the body.
Many specialized white blood cells that make up the immune system purify the body's tissues, seeking to identify pathogens and destroy them. When they identify the pathogen, immune cells should cause inflammation and attract more immune cells to the site of the introduction of pathogens. A strong immune response depends on effective interaction between immunocompetent cells. In many ways, the outcome of a viral attack is determined by the human immune system. There are people who suffer from all possible viral infections every season. And there are those who have opposed them for many years. A strong immune system is such a kind of internal passport of a person. With a healthy immune response in vaccinated people, initial inflammation attracts virus-specific T cells to the site of infection, where they can destroy infected cells before the virus spreads. Neutralizing antibodies in these people can block viral infection, and alveolar macrophages recognize neutralized viruses and purify them by phagocytosis. In general, these processes lead to purification from the virus and minimal damage to the lungs, which ensures recovery.
Various immunocompetent cells of the lymphoid (B- and T-lymphocytes) and myeloid (neutrophils, monocytes, dendritic cells, etc.) series take part in the development of the immune response. Differentiation, maturation and complex interactions between these cells during the immune response are mediated by cytokines. Protection of the body from infection is carried out by the systems of innate and acquired (adaptive) immunity. These systems are based on different principles. Innate immunity functions based on inflammation and phagocytosis. Acquired – uses antibodies and immune lymphocytes.
The immune system has a bidirectional way of defending against coronavirus attacks, using an innate immune response and an adaptive immune system.
The innate immune system is an embedded, shared immune system that immediately activates against an unrecognized virus. This system includes physical barriers such as skin, defense mechanisms such as tears and bile, and cellular responses such as inflammation caused by an influx of white blood cells capable of destroying infected cells. It is always ready to work and takes effect non-specifically as soon as any foreign object, including viruses, is detected in the body. And in relation to viral infection, innate immunity functions, relying primarily on inflammation and phagocytosis.
Adaptive or acquired immune response is a powerful second echelon of specific protection: it has various subpopulations of T cells that destroy infected cells, macrophages that remove the remnants of the cell matrix and present antigenic information to B cells, which, turning into plasma cells, produce antibodies (proteins that neutralize the virus based on its unique form). Acquired immunity uses antibodies and immune lymphocytes.
But in the case of coronavirus, this other component is needed – acquired immunity, which includes 2 mechanisms.
The first is the ability to produce antibodies that stick to the virus and restrain its spread in the body. The second is the presence of so–called T-lymphocytes, which recognize and attack infected cells.
To activate the acquired immunity , it is necessary to order 10 days for the body to start producing antibodies to the coronavirus, after which the most severe patients will develop a strong immune response. Acquired immunity uses antibodies and immune lymphocytes developed for a specific pathogen and represents a powerful second echelon of specific protection.
In response to the invasion of viruses, a cascade is launched cytokines that regulate the strength and quality of the immune response. Cytokines of innate immunity include cytokines that control the response to viral infections (IFN-α and IFN-β), stimulate the proliferation and activation of NK cells (IL-12 and IL-15), activating macrophages (IFN-γ) and inflammatory mediators (TNF-α, IL-1 and chemokines). Acquired immunity cytokines control the proliferation and differentiation of lymphocytes after antigen recognition in the early phase of the immune response, and also activate specialized effector cells (mononuclear phagocytes, neutrophils and eosinophils) to eliminate antigens in the late (effector) phase of the immune response.
Cytokines involved in the formation of an inflammatory immune response are divided into pro-inflammatory (IL-1α, IL-1β, IL-18, TNF-α, IFN-γ, IL-8 and IL-12), anti-inflammatory (IL-4, IL-10, IL-13, IFN-α and TGF-β) and representatives of the IL-6 family, whose functions are ambivalent and depend on the phase of the immune response. Proinflammatory cytokines are responsible for the induction of fever and muscle tissue catabolism, activation of mononuclear phagocytes, stimulation of acute phase protein synthesis and provide an inflammatory process leading to the destruction of the pathogen. Anti-inflammatory cytokines play an important role in limiting the development of inflammation and in maintaining homeostasis during an inflammatory reaction. As a rule, they inhibit the synthesis of pro-inflammatory cytokines. The imbalance between pro-inflammatory and anti-inflammatory cytokines is of key importance in the development of autoimmune conditions, chronization and progression of inflammatory diseases.
Currently, it has been shown that influenza A viruses cause the production of chemokines (RANTES, MIP-1α, MCP1, MCP-3 and IP-10), pro-inflammatory (IL-1β, IL-6, IL-18 and TNF-α) and antiviral (IFN-α, IFN-β) cytokines.
Features of coronavirus immunity
The stronger the collision of acquired immunity with infection, the higher the probability that in the future a person will be protected from re-infection with the same virus. But it is still not completely clear whether those who have suffered from the disease in mild form or even asymptomatic, will be able to develop a sufficiently stable mechanism to counteract the infection of the same type in the future.
Information on immunity to SARS-CoV-2, both in terms of the pathogenesis of COVID-19 disease and for the development of an effective vaccine, remains limited due to the novelty and poor knowledge of the virus. But developing a vaccine and predicting how the coronavirus pandemic will unfold until such a vaccine becomes available depends on understanding whether the immune system can provide a substantial and lasting response to SARS-CoV-2 and what effects on coronaviruses and the human body will provide a reliable level of protective immunity. The results show that almost everyone who recovered developed antibodies, regardless of age, gender or severity of the disease.
Joint research of the Center for Research on Infectious Diseases and Vaccines and the La Jolla Institute of Immunology (La Jolla Institute for Immunology), begin to fill a huge gap in knowledge and provide the first data of cellular immunology.
They also showed that in 100% of cases on COVID-19 both antibodies and immune CD4 T cells were produced. It was also found that CD4+ T-cell responses to the spike protein of coronavirus spikes, the main target of most vaccination attempts, were stable and correlated with the titers of anti-SARS-CoV-2 IgG and IgA.
"All efforts to predict the best vaccine candidates and precise pandemic control measures depend on understanding the immune response to the virus. People were very concerned that COVID-19 does not cause immunity, and reports of re-infection have increased these fears, but now the knowledge that an ordinary person gives a solid immune response should largely put an end to these fears. If it is difficult to develop long-term immunity to the virus , then it will not be easy to develop a vaccine against it. Or the vaccine will be different: for example, it will need to be applied not once for a lifetime, or once every 5, 10 or 15 years, but every year, as in the case of the flu. Then the coronavirus vaccine it will also be included in the vaccination calendar. And the very duration of immunity, regardless of whether it was developed with a real disease or vaccination, will let us know whether we can contain the spread of this virus," said Crotti, professor at the Center for Research on Infectious Diseases and Vaccines.
Often, the most stable immunity is obtained by patients with a severe course of the disease, and these are superhumans who have such a powerful immune response that their antibodies can be used to treat others with convalescent plasma, which is now being done. There are about 7-8% of them. But there are also cases when there are no antibodies in the human body after the disease – also about 7-8%. They had an elevated body temperature and cough, but no antibodies to the coronavirus. This means that they got rid of the infection with the help of interferons, which are rapidly produced in the human body in response to the virus. In this case, interferons coped by themselves and antibodies did not arise, because these patients do not have long-term stable immunity to COVID-19. At least 40% of those who have been ill have a fairly low level of antibodies. And for some, immunity is noticeably reduced within a month and there is a risk of re-infection.
With a standard viral disease , the innate immunity begins to work immediately after infection, destroying the infection and the so-called target cells damaged by it. Thus, further spread of the virus is prevented and the body is cleansed. If the infection remains, then adaptive immunity is triggered after some time.
As the researchers found out, in the case of coronavirus , acquired immunity is activated even before all the target cells of the upper respiratory tract are destroyed. This does not allow the innate immunity to quickly cope with the infection and does not lead to an overload of the immune system.
Longer viral activity can trigger an overreaction of the immune system, called a cytokine storm, which kills healthy cells, causing tissue damage.
According to Chinese researchers, the interaction of innate and adaptive immunity temporarily reduces the viral load on the body, which is why patients experience short -term improvement.
However, if the body is not completely cleared of the virus, and the target cells recover, the infection can attack it again and reach another peak. That is why in some patients with COVID-19, symptoms subside for a while, and then a relapse occurs.
The immune system must be in balance: too weak a response is bad, and too strong is also bad. A strong immune system in the case of a coronavirus infection can play a cruel joke with a person, because the autoimmune response itself can pose a danger . In certain cases, the autoimmune reaction must be suppressed so as not to aggravate the patient's condition. In such cases , immunosuppressive drugs are prescribed.
In many infectious diseases, pathology, including leading to severe conditions and even death, is caused not by the infectious agent itself, but by an inadequately strong reaction of the immune system to the pathogen. This can be called a complication, but the more correct term is immunopathology. An extreme example is a severe allergic reaction: this is also an immune reaction, and it is for the body much more dangerous than the pathogens of allergies themselves.
Cytokine storm is an example of such pathology. Molecules that should regulate the inflammatory and immune response, acting in small doses and in specific areas of the body, are produced systematically and in high concentrations. Cytokine storm, – uncontrolled and not carrying a protective function of excessive cytokine production. This phenomenon has been well studied in highly pathogenic human influenza A/H5N1 viruses, which are characterized by a high degree of lethality, largely caused by hypercytokinemia. And with a severe coronavirus infection, doctors also observe a cytokine storm.
The reasons why some infected with SARS-CoV-2 do not show symptoms of the disease, while others develop acute pneumonia, are due to the genetic type of the immune system. The main cause of death of people from COVID-19 is acute respiratory distress syndrome (ARDS), as a result of which fluid fills the lungs and disrupts breathing. Elderly people and people with chronic diseases are most susceptible to it.
Aggressive immunity is the cause of pneumatoses caused by coronavirus. There is a cytokine storm in the lungs, thrombosis is formed, the alveoli cannot be actively filled with air, a respiratory problem begins, which can lead to death. In such a situation, it is more important not to create a strong immune system, but the ability of lymphocytes to identify the virus as an enemy for the body.
Previously, scientists at Boston Children's Hospital (Boston Children's Hospital) and the Massachusetts Institute of Technology (Massachusetts Institute of Technology) in the USA found out that interferon – one of the main protective systems of the body – was ineffective against SARS-CoV-2 and, conversely, causes the development of the disease. It also turned out that interferon, which is involved in protecting the body from most viruses, stimulates the production of ACE2, giving the coronavirus new opportunities to penetrate into human respiratory tissues. Thus, the virus affects the lungs.
Chinese scientists conducted a study and found out that carriers of the second blood group were the most vulnerable to SARS-CoV-2 , but people with the first group showed maximum resistance to the virus .
Individual coronavirus susceptibility
The asymptomatic course of COVID-19 can be more than 50% of sick citizens, and this is mainly determined by the state of immunity of each individual. Their exact number can be determined only after universal testing. The fact is that the human immune system can be strong enough to immediately perceive the virus entering the body as a danger and begin to build protection against it. As a result, the symptoms that we see in other patients are absent. There are no manifestations of coughing, an increase in body temperature, a decrease in saturation (oxygen saturation of the blood).
The number of viruses that attack the human body is defined by the term "viral load". The outcome of the meeting depends on the initial dose of the infecting agent. A high dose will break through the protection, with a small portion of the virus, the innate immunity will do well by itself, "swallow" and we won't even feel it, the second level of acquired immunity may not reach work and it won't work.
But if, figuratively speaking, 10,000 viruses pounce, then even the healthiest immunity will clearly "not be well." That's why you need to avoid crowded places and close communication and use a protective mask in such places, otherwise immunity will have to work in an enhanced mode. As they say, "10 times 10 is better than 500 times once."
Some people are "aerosol super-distributors" of coronavirus. After them, there are much more particles in the air than after the rest. Why this happens is not yet fully known, but they create a serious viral load for others, which can lead to high-intensity infections. Preliminary studies have shown that the low level of viral clearance in such people is determined by the areactivity of their immune system, which leads to a longer and massive viral contamination.
There are 70-80% of asymptomatic carriers of coronavirus in the world. Such people eventually become a kind of "vaccine", since they will be the first to develop antibodies to the virus.
These individuals also become asymptomatic carriers due to genetic immunity, the body of some people simply "does not read" these viral particles, for example, due to the lack of receptors for the virus. Such groups of people were also identified in other infections. For example, in the 2000s, Kenyan prostitutes were investigated, who were not protected, but also did not get HIV. This was explained by genetic racial characteristics.
With tick-borne encephalitis, there were also certain groups of people who simply did not have symptoms of the disease. At the same time, their body produced antibodies to the infecting virus.
Chinese researchers in a large sample (6,764 people) found that only 20% of those infected with coronavirus showed symptoms, and 80% felt absolutely healthy, but they were infected, which was confirmed by testing. At the same time, all asymptomatic infected remain contagious to others and continue to spread the infection without suspecting it. New data from Chinese doctors confirm the most pessimistic estimates about the extent of infection. A number of virologists from Australia and the UK also believe that the real number of cases of COVID-19 infection in the world is most likely 10 times higher than the detected cases of infection, since doctors do not record asymptomatic infections. If today doctors have already recorded 5.6 million coronavirus patients worldwide, then in reality there are about 56 million.
An unpleasant feature of the asymptomatic spread of the virus is the inability to track and interrupt all chains of infection. The virus can pass through 4 asymptomatic carriers and give a high body temperature and other clinical signs of the disease in the 5th. How to deal with this is still completely unclear. Elusive symptoms are also demonstrated by elusive immunity among people who have already been ill – some carriers detect antibodies by enzyme immunoassay (ELISA), and some do not, although tests by polymerase chain reaction are positive.
In order for a virus to infect a sensitive victim, it must be able to attach to a receptor protein, which is called a "traitor protein".
In the human body, such a protein for SARS-CoV-2 the ACE-2 protein became. It is produced by our body mainly with age and in the presence of serious cardiovascular diseases. The older a person gets, the more ACE-2 protein is expressed on the surface of the alveolar cells of the lungs. The younger the person, the less ACE-2 protein. That's why young children practically do not get sick with coronavirus, and children over the age of 9 carry it like a regular seasonal flu. SARS-CoV-2 also invades cells by binding to the CD147 receptor on the cell surface. The virus binds to cells using its own SP protein, which was confirmed by immuno-electron microscopy. The peculiarity of this virus is that the proteins located on the spikes for the body are first determined not as enemies, but as normal cells, so they initially let it into the cell, where it begins to actively multiply.
Sometimes it is not clear why suddenly one patient has a high body temperature for 2-3 days, and then he quickly recovers. And the other, with a successful course, suddenly an exacerbation begins on the 7-8 day. This is largely determined by the characteristics of immunity. This virus is dangerous for people over the age of 60, people with chronic diseases of the cardiovascular system, lungs and bronchi, diabetes mellitus and unpleasant for adults because of the characteristics of the ACE-2 protein. Therefore , the child can continue to live his normal life, but become an accidental viral "postman" for grandparents.
Cross-immunity exists
The leading virologist of the Berlin clinic Charite Christian Drosten cited interesting data according to which those who had previously been ill with any "colds" coronaviruses (4 varieties that have long caused seasonal acute respiratory diseases) are not related to to SARS-CoV-2, may have immunity to COVID-19. According to him , T-cells of people who have not yet suffered from COVID-19 disease were examined for reactivity to the new coronavirus. "It was found that 34% of patients had reactive T cells, although they had never had contact with SARS-CoV-2," said K. Drosten.
According to the virologist, the studies he mentioned in the clinic's laboratory showed that a number of coronaviruses that cause colds have "similar sites" with SARS-CoV-2. In addition, they can stimulate T cells, which to a certain extent resist both coronaviruses that cause colds and SARS-CoV-2.
Interesting similar data were obtained at the Center for Research on Infectious Diseases and Vaccines, the Institute of Immunology La Jolla and the University of California at San Diego (University of California San Diego) when studying samples of frozen leukocyte mass people in the United States, taken in 2015-2018, who could not be exposed to the virus that first appeared in China at the end of 2019.
Researchers have found that important immune cells in the blood of these patients, called CD4+ and CD8+ T-lymphocytes, several SARS-CoV-2 proteins were recognized in 40-60% of cases. They included spike, the spike protein that gives the virus its characteristic appearance, but also included proteins called M, N, etc. One possibility to explain this phenomenon is cross–immunity. There are 4 coronaviruses that cause colds in humans. It is possible that cells that react to cold coronavirus proteins may be cross-reactive to SARS-CoV-2 proteins.
Cases of asymptomatic course of the disease can be explained by the presence of cross-immunity in some part of the population resulting from the disease of other types of coronaviruses, as a result of which "the pandemic will end faster," and this is good news.
No less sensational news is that the researchers managed to find in the samples of the European blood bank for the period in the summer of 2019, that is, before the official outbreak of the epidemic in China, antibodies to SARS-CoV-2, which can be explained either by cross-immunity, or by the earlier appearance of SARS-CoV-2 than China has notified about it.
Immune certification
The governments of some countries believe that the presence of antibodies that are produced in the human body after infection with coronavirus can serve as a basis for issuing him a so-called "immunopassport", indicating his resistance to infection. Such passports can give a sick person the right to move or go to work.
According to the idea of this innovation, those who had antibodies to SARS-CoV-2 detected during testing could be allowed to go to work safely. This would be especially useful in the case of nursing home workers and hospital staff who are constantly in contact with people at high risk of becoming seriously ill.
The Chilean authorities have announced that they plan to issue " health passports" to those people who have been ill with COVID-19. It was noted that they will be able to go to work after an antibody test, which will show their immunity to the virus.
In Russia, where testing amounts to hundreds of thousands per day, it is also believed that thanks to antibody tests, it will be clear that a person can, for example, move freely and go to work. And then it is appropriate to issue "immunity passports" or "risk -free certificates" for those who have been ill. The ELISA test system, which detects antibodies to the new coronavirus, helps to understand whether a person has had contact with the virus itself, as well as to assess population immunity and study the effectiveness of vaccines being developed.
The idea of creating an "immune passport" may be followed by norms that only people will be allowed into public places people who are immune to SARS-CoV-2. With antibodies, you can fly on airplanes, go to restaurants and theaters. Pilots, waiters, actors will work with them... and people without antibodies will live in reservations, where those with antibodies will deliver food and medicines (provided that the other diseases will not be legally abolished). After the pandemic, special documents may appear for tourists.
Thus, the Madrid Association of Hoteliers (Asociación Empresarial Hotelera de Madrid is already considering the possibility of introducing a certificate "Hotels without COVID-19" (COVID-19 Free Hotel), which will guarantee that there are no coronavirus infected among the staff and guests. At the same time, the introduction of an "immunity passport" with information about the presence of antibodies to coronavirus in the tourist is also being discussed in the UK.
In addition, the measures already implemented by some airlines may continue to operate after the pandemic. For example, in the airline Emirates has introduced a mandatory blood test for all passengers, which detects the presence of infection in 10 minutes. At the same time, some countries already allow only travelers with health certificates into the country. There was a proposal to issue immune passports to tourists, and people who have been ill with COVID-19 will be able to get them. So, the residents of Chile have already begun to issue this document. However, not all doctors appreciated the offer, because it is not yet clear whether re-infection with the virus is possible.
But then the practice should be introduced in the countries maximum testing coverage. However, although almost every sick person with a pronounced clinical picture has antibodies in the blood, not all of them are the same. To do this, it is necessary to identify neutralizing antibodies that attach to the coronavirus and prevent it from infecting new cells.
A survey of recovered patients in China showed that 30% of them had extremely low levels of such neutralizing antibodies.
That is why, according to WHO, protective immunity at the cellular level can also be an extremely important factor in recovery , and its certification is already a more complex and expensive procedure.
The Ministry of Health of Ukraine, having prepared an appropriate order, plans large-scale ELISA testing to understand how many Ukrainians have already been ill, including asymptomatic cases. If immunoglobulins M (antibodies of the lgM class) are detected, then the person is in the stage of the disease, and he is dangerous to others, if immunoglobulins G (antibodies of the lgG class) are detected, it means that he has already encountered a new coronavirus, does not pose a threat to others and, most likely, will not get sick anymore, but there is no 100% guarantee. The Ministry of Health does not mention the issuance of health passports.
First of all, people from risk groups who are in the "red zone" of contacts with a large number of people with possible infection will be tested for free – medical personnel, workers The National Police and the National Guard, as well as patients with pneumonia and with symptoms of coronavirus. The research will be conducted in municipal and public health institutions. All other categories of the population can satisfy their curiosity about possible infection in private laboratories for 600-800 UAH.
Vaccination against infection caused by the new coronavirus SARS-CoV-2
The disclosure of the genome of the new coronavirus SARS-CoV-2 has given a powerful impetus to the biotechnology industry in its attempts to develop vaccine products against this infectious disease. In total, at the beginning of May , there were about 100 projects in different parts of the world to create a vaccine against COVID-19 , and 10 vaccines are already in the phase of clinical trials. Of these, 2 in the USA, 4 in China, 2 in Russia, 1 in the UK and 1 in Germany.
It is clear that vaccines against SARS-CoV-2 can see the light only if their development receives an impressive boost from the state. The cost of developing a vaccine against an epidemic infectious disease, the amount of costs that will be required to carry out a vaccine candidate from preclinical studies to the end of phase IIa clinical trials, ranges from 30 to 70 million US dollars. Taking into account the risk of failures of vaccine candidate drugs, and if licensing costs and indirect costs are taken into account, this amount increases significantly - up to $ 319-469 million.
However, it has only now become clear that the necessary investments simply pale in comparison with the losses that the global economy will eventually suffer from the pandemic, not to mention human resources.
In 1919, the "Spaniard" claimed 100 million lives. It's the flu H1N1. He is still among us today. It came 100 years ago from animals (like the new coronavirus), and remained among people. The population is partially protected from it by innate immunity. But not completely, tens and hundreds of thousands of people die from H1N1 every year. Despite the fact that there is a vaccine for it! It is an integral part of all flu vaccines.
The world has become vaccine–dependent, and the situation with vaccine–controlled infections is as follows: measles (there is a vaccine) - 140 thousand deaths per year, pneumococcus (there is a vaccine) - 2-2.5 million deaths per year, hepatitis B (there is a vaccine) – 650 thousand deaths per year, tetanus (there is a vaccine) – 89 thousand deaths per year, rotavirus (there is a vaccine ) - 800 thousand deaths per year, cervical cancer (there is a vaccine) – 250 thousand deaths per year, tuberculosis (there is a vaccine) – 1.5 million deaths per year, influenza (there is a vaccine) – (from) 650 thousand (to) 1 million deaths per year, COVID-19 (there is no vaccine) – 350 thousand dead today. And "it's not evening yet", the process is underway and the statistics are steadily growing.
When creating a vaccine against the new coronavirus SARS-CoV-2 , we are talking about exceptionally advanced and rapid approaches, and not any traditional ones that require long and tedious processes for decades. Some of them are turning to technologies that have never been used before in current approved vaccines, others have not been previously studied in humans.
In the race to create a vaccine against coronavirus SARS-CoV-2 (the causative agent of COVID-19) involved more than 50 major biopharmaceutical companies from different countries. More than 100 vaccine prototypes are in development. The USA and China are fighting for the primacy in creating a vaccine , the latter is still leading in this race, since they joined the work 2 months earlier.
In the USA, they took the accelerated path of creating vaccines using modern international experience – they switched to clinical trials in humans after a short experiment on mice, actually skipping all stages of preclinical studies, considering that in a pandemic it is quite acceptable. By following WHO protocols, scientists can also speed up their work in phases II and III of vaccine research.
NIAID: Government funding
Research conducted in academic institutions is sponsored by the National Institute of Allergy and Infectious Diseases USA (National Institute of Allergy and Infectious Diseases).
CEPI: the main non-governmental sponsor of immunobiological developments
The Coalition for Epidemic Preparedness Innovation (CEPI) is a non– profit organization established in January 2017, currently sponsored by the governments of Norway, Germany and Japan, the Bill & Melinda Gates Foundation (Bill & Melinda Gates Foundation), the Wellcome Trust Charitable Foundation and the European Commission.
CEPI has set a very bold goal to get a vaccine ready for human trials in just 16 weeks. This statement is quite feasible. According to the experience of the previous SARS-CoV epidemic, it took 20 months to create and bring a trial DNA vaccine to phase I clinical trials , and in the future for other viral diseases, the desired time frame reduced to more than 3 months. And mRNA-based vaccines require even less time.
CEPI hopes that in six months a working vaccine for the prevention of coronavirus infection COVID-19 will be ready from one or another developer.
For reliability and given the importance of the pandemic threat, the funding was "spread out over a large number of baskets" in the 100% hope of choosing the best from the set.
Moderna Inc. and innovative mRNA vaccines
In the USA based in In Massachusetts , the biotechnology company Moderna, in collaboration with the National Institute of Allergy and Infectious Diseases, produced the mRNA-1273 vaccine against SARS-CoV-2, conducted preclinical studies that showed good safety and efficacy (immunogenicity) in laboratory animals. Moderna has started phase I clinical trials before the completion of preclinical animal studies, which goes against the requirements of regulators, and on May 7 announced that it had received permission The US Food and Drug Administration (FDA) is promoting its candidate vaccine in a phase II study, which should be followed by a phase III study in the fall – and this is an unthinkable speed of vaccine promotion. Participants do not risk anything, because the vaccine does not contain a whole virus. The aim of the study is to identify side effects, after which more extensive clinical studies will be conducted.
On May 18, Moderna announced the successful completion of Phase I clinical trials of an experimental mRNA vaccine (mRNA-1273). During clinical studies, scientists revealed that the vaccine is generally safe, well tolerated by the body and all participants developed antibodies against this virus in their blood.
The data on immunogenicity for the administered doses of 25 mcg and 100 mcg (in the group of 18-55 years) were studied for double administration and dose 250 mcg (in the group of 18-55 years) with a single administration.
The analysis of the response showed that the number of protective antibodies in the blood, depending on the dose of the vaccine administered, it exceeded or was at the same level as in people who had already had a coronavirus infection.
Of the side effects of the vaccine, one person was found to have erythema around the injection site (he was given a dose of 100 mcg). The redness was temporary and disappeared by itself. Local side effects were observed at a dose of 250 mcg in 3 participants, and then only after the 2nd dose.
Based on the interim phase I data , adjustments will be made to the Phase II study. For the phase III study , the vaccine dose will be chosen between 25 and 100 micrograms. The start of these studies is scheduled for July.
It remains to be seen what level of antibodies will give protection against SARS-CoV-2 and how long this protection will last. The results of phase I give grounds to study in more detail doses of 50 micrograms and not to use above 250 micrograms, which can help in saving money and vaccines, as well as produce large volumes of it for more people without compromising the effectiveness of vaccination.
The phase II study will be designed to assess the safety, reactogenicity and immunogenicity of double mRNA-1273 vaccinations with an interval of 28 days in volunteers. Each option will be assigned a placebo, a vaccine dose of 50 or 250 mcg for both vaccinations. Moderna intends to register 600 healthy participants in 2 groups of adults aged 18-55 years (n=300) and elderly people – 55 years and older (n=300). Participants will be monitored for 12 months after the second vaccination.
Stefan Bansel, CEO of Moderna, said that the FDA is also finalizing the protocol for the Phase III study of mRNA-1273, which is scheduled to begin in June 2020. The mRNA-1273 vaccine has received the designation "accelerated mode" and is entitled to the status of "priority review", which accelerates the regulatory review process, according to which the FDA seeks to make a decision on the approval of the drug within 3-6 months. In February, Moderna received funding in the amount of $ 483 million. from a U.S. government agency to accelerate vaccine development.
mRNA-1273 is a new encapsulated mRNA vaccine (messenger RNA, or transfer of a fragment of the RNA genetic code of the virus) with lipid nanoparticles (LNP) encoding a spike protein form stabilized before fusion. Technology transfer is expected to begin in June, and the first batches of mRNA-1273 will be manufactured at the Lonza plant in the USA in July.
The vaccine uses matrix RNA (mRNA) technology, which instructs cells in the body to produce specific coronavirus proteins, which then trigger an immune response. The approach can be used in many types of treatment, but has not yet been approved for any medication. In the case of vaccine preparations, mRNAs encode proteins-antigens of a given pathogen – the body reacts to them by inducing a T-cell response in the form of priming the immune system, which becomes prepared to repel an attack from a possible infection. mRNA vaccines, like DNA vaccines, have an enhanced potential in stimulating the T-cell response compared to inactivated viral or protein vaccines, since they more easily organize the presentation of antigens on HLA histocompatibility molecules necessary for the activation of the T-cell response.
As soon as this viral protein is recognized by the body, the immune system is triggered. When using the mRNA approach to the creation of vaccines, imitation of natural viral infections is achieved, similar to those with a natural viral life cycle, since the synthesis of mRNA-mediated viral antigenic proteins is carried out in the cells of the body itself. One vaccine may contain multiple mRNAs encoding multiple viral proteins. In the human body, these mRNAs give the command to produce protective viral proteins, that is, individual parts, and not the whole virus as a whole. This means that there are no dangerous toxic components of the virus. These mRNA-encoded proteins immunize the body and form a strong immune response.
mRNA vaccines are also characterized by rapid development and readiness for production and the efficiency of capital investments, the production of mRNA vaccines is carried out on the basis of a unified production common to any vaccine preparations, and only a set of mRNAs changes to switch to the production of other vaccines.
Moderna solved the difficult problem of delivering medicinal mRNA compounds to the body by modifying uridine nucleotides of mRNA and encapsulating mRNA molecules in a proprietary shell of lipid nanoparticles.
Over the past 4 years, Moderna has successfully conducted 6 prototype preventive vaccines through phase I clinical trials designed to prevent infection with cytomegalovirus, influenza virus type A subtypes H10N8 and H7N9 (both are varieties of avian influenza), respiratory syncytial virus (RSV), chikungunya fever, human metapneumovirus and type 3 parainfluenza virus (hMPV/PIV3).
The US government, in anticipation of receiving the vaccine in the fall of 2020, agreed to allocate a whopping $ 483 million. From the federal funding budget to promote the mRNA-1273 coronavirus vaccine.
Government investments will mainly go to the FDA registration process and increase production capacity. This money will also allow the biotech company to hire 150 new employees, accelerate the clinical development of the vaccine and launch a phase II clinical trial within a few weeks.
CureVac: RNA printer and mRNA vaccines
The German "Cuevac" (CureVac) is a direct competitor of Moderna, also trying its hand at therapeutic and vaccine preparations on the basis of mRNA technology. CEPI has allocated a grant to CureVac in the amount of up to $8.3 million, which will be aimed at accelerating the development of a vaccine against the new coronavirus SARS-CoV-2, its production and clinical testing.
CEPI is already financing the activities of CureVac: in February In 2019, the German company received $ 34 million for the implementation of the project of the so-called RNA printer – a transportable, low -cost, automated installation for the production of mRNA vaccines. The RNA printer is able to "print" several grams of mRNA in lipid nanoparticles in a few weeks , which is enough to produce over hundreds of thousands of doses of the vaccine. Using just 1 gram of mRNA, one million people can be vaccinated.
Based on the experience of creating the CV7202 rabies mRNA vaccine At CureVac, only 2 servings in 1 mcg of the vaccine were enough to induce a strong adaptive immune response in volunteers: the titer of protective virus-neutralizing antibodies exceeded the threshold recommended by WHO.
Due to the versatility of mRNA vaccine design, such a mobile RNA printer, easily delivered anywhere in the world, can be useful for rapid response to outbreaks of infectious diseases, while significantly saving time and money. In April, the company developed samples for animal studies, and is ready to start clinical trials in mid-summer. It is also developing mobile technology to create a vaccine so that it can be produced at the site of an outbreak of the virus.
In the midst of the coronavirus pandemic and the US election campaign, Donald Trump decided to make a deal in Germany in the spirit of his favorite slogan "America first" (America first). USA, as it became known from the publication of the German edition of Welt am Sonntag, tried to outbid CureVac virologists for $1 billion and move the company's headquarters from German to its territory Tubingen. On March 15-16, this story made a lot of noise in the German media and social networks. D. Trump, trying to buy out a German biotech company, was preparing a rescue from the coronavirus only for America, setting conditions for its exclusive distribution. The founder of the SAP software company and the owner of the biotech firm CureVac, Dietmar Hopp, stopped the attempt Washington to secure exclusive rights to a remedy against COVID-19.
At a meeting at the White House on March 2, D. Trump insisted that the vaccine be ready before the US elections in November.
The fact is that, according to the company CureVac, it will be able to start clinical trials of a promising remedy – a vaccine against the SARS-CoV-2 virus in early summer. With a favorable development of events, the vaccination could be ready by autumn. Moreover, the company reports that it has a certified in December 2019. equipment that "can produce up to 10 million vials of vaccine in one production cycle."
Minister of Foreign Affairs of the Federal Republic of Germany Heiko Maas stated that "we will be able to defeat this virus only together, and not against each other." German scientists, he pointed out, occupy leading positions in the development of medicines and vaccines, while cooperating with specialists around the world. We cannot allow anyone to try to exclusively seize the results of their scientific research. The resulting vaccine will belong to the whole world. Minister of Economy of the country Peter Altmaier and the head of the Ministry of Internal Affairs Horst Seehofer also confirmed that the German authorities will not allow other countries to appropriate exclusive rights to the developments of German virologists on the coronavirus vaccine.
Inovio Pharmaceuticals: DNA Vaccines
Inovio Pharmaceuticals, an American biotech company, has received $5 million from the government to develop a vaccine against the new coronavirus. The vaccine is called INO-4800, and each volunteer will receive 2 doses of a relatively new DNA-based vaccine candidate at 4-week intervals to test its effectiveness and safety. Developers are ready to start Phase I in University University of Pennsylvania, and by the end of the year the company promises to produce a million doses. As Inovio Executive Director Joseph Kim noted, the company managed to create a vaccine in 3 months in compliance with all regulatory requirements, speeding up the creation process. According to him, the company cooperates with the FDA in the field of design development of the II and III stages of clinical trials. Stage II may begin in the summer.
40 healthy volunteers will take part in phase I clinical trials of the INO-4800 vaccine . Each of them will receive 2 doses of the vaccine with a difference of a month. According to the company, data on the early immune response and safety of the vaccine are expected in early summer.
The development of Inovio Pharmaceuticals is presented DNA vaccines encoding pathogenic antigens. As part of the SynCon process , a corresponding DNA sequence is generated for ribosome loading and expression of antigenic proteins. The vaccine preparation, which is a plasmid in which a ready-made DNA sequence is embedded, is intended for subcutaneous or intramuscular administration. In order for plasmids to penetrate into cells, a Cellectra device is used, which organizes several short-term electrical impulses and forces cell membranes open up. After a few hours or days, the cells begin to synthesize antigens – their presentation to the immune system activates the production of antibodies and the generation of T-killer cells, "charging" the body with readiness for a possible viral attack.
DNA vaccines are characterized by an undoubted number of advantages over traditional corpuscular vaccines and are generally similar to those for mRNA vaccines.
Five DNA vaccines undergoing Phase I clinical trials have been collected at Inovio Pharmaceuticals experimental sites: against HIV, Ebola, Zika, Lassa and MERS-CoV viruses. The last one, INO-4700 (GLS-5300), tested jointly with Korean GeneOne Life Science, showed high efficacy: among those who received 2 or 3 doses of the vaccine , seroconversion was recorded for 86 and 94% of participants, respectively, neutralizing antibodies – 50%, T-cell responses – 71 and 76% accordingly. After 60 weeks of observations, humoral and cellular responses induced by the vaccine were recorded in 77 and 64% volunteers, respectively.
A grant of up to $9 million allocated by CEPI will be used for preclinical study and phase I clinical trials of the experimental DNA vaccine INO-4800 against SARS-CoV-2. Agreements have been reached with China's Beijing Advaccine Biotechnology to accelerate research.
If we compare DNA vaccines with mRNA vaccines, the latter are still more optimal: they only need to cross the plasma membrane to start the production of protein antigens – the former must additionally bypass the nuclear envelope, which reduces the final effectiveness. But the advantage DNA vaccines consist in their greater stability, that is, they are more practical in terms of distribution in developing countries and rural areas that do not have proper storage infrastructure.
GlaxoSmithKline (GSK) and Sanofi
According to a statement released on Tuesday, April 14, pharmaceutical companies GlaxoSmithKline (GSK) and Sanofi announced cooperation in the development of a vaccine against COVID-19, clinical trials of which will begin in the second half of 2020, CNN reports.
"Sanofi and GSK have signed a letter of intent to collaborate to develop an auxiliary vaccine for COVID-19, using innovative technologies from both companies to help combat the pandemic," the statement said.
The companies report that unprecedented cooperation 2 The global vaccine manufacturing giants will lead to the creation of a "joint working group on cooperation", which will seek to mobilize the resources of both companies to accelerate the development of a vaccine. GSK and Sanofi have agreed that any vaccine developed as a result of their collaboration will be available to the public in all countries.
Sanofi and Translate Bio
Sanofi Pasteur, the vaccine division of Sanofi (Sanofi), and the biotech company Translate Bio, which carries out clinical trials of drugs based on mRNA, have agreed to jointly develop a new mRNA vaccine for the prevention of COVID-19.
Translate Bio is already creating many concepts based on mRNA. The company will use its own mRNA platform for the research, development and production of candidate vaccines against the SARS-CoV-2 virus.
Sanofi's contribution to the collaboration will be experience and knowledge in vaccine development and support from external research networks. This will facilitate the accelerated passage of research phases by candidate vaccines.
For Sanofi, this is the second partnership aimed at developing a candidate vaccine against COVID-19. In February 2020 the company announced cooperation with the Office of Advanced Biomedical Research and Development (Biomedical Advanced Research and Development Authority – BARDA) of the U.S. Department of Health and Human Services in this area. As part of the agreement with BARDA, Sanofi will begin research on a vaccine based on a recombinant protein for the prevention of COVID-19.
The mRNA platform created by Translate Bio has advantages over older platforms for the exploration and research of viral proteins. The old platforms were based on research using cell cultures, the results of which were reliable, but the research itself took a lot of time. The mRNA platform allows you to quickly determine the nucleotide sequence of RNA-containing viruses and identify antigens (viral proteins) that can enhance the body's immune response against pathogens of certain diseases.
MIGAL
The Israeli MIGAL Research Institute has been working for 4 years on the creation of a vaccine against a different type of coronavirus – the one that is common among chickens. Faced with a new coronavirus from Wuhan, scientists used previous developments and revealed that their veterinary product has cross-protection against SARS-CoV-2. The antigens created by the laboratory can cause not only a general immune reaction of the body, but also stimulate the local production of antibodies at the site of infection.
Currently, the MIGAL Institute has conducted preclinical studies that have demonstrated a high level of antibody production against a new coronavirus infection, and specialists have started clinical studies.
China
Chinese virologists are developing 5 variants: based on nucleic acids, adenovirus vector, recombinant, inactivated and live attenuated (based on weakened virus).
Three vaccines are already at the stage of clinical trials. One of them, a joint development of CanSino Biological Inc. and Beijing Institute of Biotechnology, a vaccine based on the adenovirus vector, is undergoing phase II clinical trials in a laboratory in Wuhan.
Scientists of the Wuhan Institute of Virology (Wuhan Institute of Virology) at the Chinese Academy of Sciences and Wuhan Institute of Biological Products (part of Sinopharm Group).
A Beijing company has also started a study of its drug on volunteers Sinovac Research & Development Co.
Specialists of Dongfang Hospital at Shanghai University Tongji (Tongji University) and Chinese biotech company Stemirnas synthesize matrix ribonucleic acid (mRNA) with several sequences of different antigens.
Scientists from The University of Hong Kong has created a vaccine against the COVID-19 coronavirus by modifying the vaccine against the common flu, to which a part of the coronavirus surface antigen was added. Virologists believe that the new vaccine will protect against both seasonal flu and the new coronavirus. The development is undergoing preclinical studies.
CanSino Biological Inc. and Beijing Institute of Biotechnology
The Chinese company CanSino Biologics, located in Tianjin, was the first company to develop a vaccine against COVID-19, She was the first to introduce the vaccine into phase II clinical trials and was the first to publish peer-reviewed data from a phase I study of a vector vaccine against COVID-19 based on type 5 adenovirus, called Ad5-nCoV.
A single dose of the vaccine can cause a pronounced immune response with an increase in the high titer of binding antibodies to a live virus, depending on whether the test volunteers received low, medium or high doses. It was found that the vaccine rapidly elicits an antigen-specific T-cell response in most participants, with cellular and humoral responses being slightly higher in those who received a higher dose. The authors wrote that there is a strong correlation between the concentrations of binding and neutralizing antibodies.
Local pain at the injection site, fever, headache and fatigue were the most common side effects of moderate severity. Severe events were "temporary and self-limiting" and similar to those observed with the use of another Ad5 vector-type vaccine tested against the Ebola virus.
In the II phase of research that takes place in China and in Canada, low and medium doses are tested, respectively, 50 and 500 billion viral particles.
In addition, earlier this week, CanSino announced an agreement with Precision NanoSystems, a Vancouver-based company, to develop a lipid nanoparticle mRNA vaccine against COVID-19.
In addition, CanSino Biologics, in collaboration with Precision NanoSystems, is also testing another mRNA recombinant coronavirus vaccine in China.
The duo will work on a vaccine against lipid mRNA nanoparticles for SARS-CoV-2. Precision NanoSystems is developing a vaccine, and CanSino is engaged in preclinical and clinical development, regulatory activities and commercialization. CanSino has the rights to sell the vaccine in Asia, with the exception of Japan, while Precision, based in Vancouver, retains the rights to the rest of the world.
Chinese Clover Biopharmaceuticals together with the British giant GSK
Company Clover Biopharmaceuticals synthesizes the active substance: protective proteins – antigens that trigger the immune response necessary to protect against the virus. GSK provides so–called adjuvants, which are chemical compounds that enhance this immune response and the effectiveness of the vaccine. GSK has entered into a similar partnership with the Australian University of Queensland (University of Queensland) and cooperates with the CEPI Foundation.
Chinese epidemiologists conducted a series of vaccine tests from coronavirus infection, including with the participation of volunteers.
The recombinant drug based on the adenovirus vector demonstrated good results at the previous stage of preclinical testing – with the participation of laboratory animals.
More than a hundred volunteers participate in the stage of clinical trials . They were divided into 3 groups. Each patient will receive different doses of the vaccine. During and after the 2-week quarantine, volunteers are waiting for medical examinations and tests. Then the participants of the clinical trials will be monitored for at least another six months.
Pfizer and BioNTech
The American pharmaceutical company Pfizer and its German partner BioNTech are working together on 4 candidates for mRNA vaccines. They have also started clinical trials of their BNT162 candidate vaccine. Their vaccine candidate is based on a specially developed messenger RNA (similar to the Moderna vaccine), clinical trials are being conducted in the USA to test the vaccine and they plan to test a potential vaccine on 360 healthy volunteers.
BioNTech Johnson & Johnson and Pfizer Inc, which are working with Germany's BioNTech SE, are also developing vaccines against the new coronavirus.
Pfizer CEO Albert Burla said that his scientists will be able to finish developing the vaccine in the fall. He stressed that human studies will take place in August.
AstraZeneca
The US will allocate $ 1.2 billion to finance the development of a potential vaccine against COVID-19 and order 300 million doses from the British AstraZeneca. The agreement implies conducting clinical trials in the United States with the participation of 30 thousand patients this summer.
As stated by the Minister of Health and Human Services USA Alex Azar, he hopes that the first doses of the vaccine being developed AstraZeneca, together with the University of Oxford, will arrive in the USA in October 2020, and full deliveries will be carried out by the beginning of 2021.
Under the terms of the financing agreement, the Office of Advanced Biomedical Research and Development of the U.S. Department of Health and Human Services (HHS) will pay the company $ 1.2 billion to support further clinical research and other purposes, including capacity building.
AstraZeneca has also signed a contract with the government Great Britain for the supply of 100 million doses. The company plans to start delivery in September 2020.
According to a statement from the British government, it intends to purchase 1 billion doses of the vaccine in the current and next years if clinical trials are successful. The statement also states that the vaccine is being investigated for use in pediatrics and AstraZeneca cooperates with international organizations, including WHO, in order to distribute the potential vaccine fairly in all countries of the world.
University of Queensland: Molecular Fusion Proteins
All enveloped viruses, such as, for example, coronaviruses, influenza virus or respiratory syncytial virus, require the fusion of the viral and membrane of the host cell in order to penetrate into the latter and infect it. This process is facilitated by viral fusion proteins: by their own structural rearrangement from a metastable conformation "before fusion" to a highly stable conformation "after fusion". Viral fusion proteins, or fusogens, are the main targets of protective reactions of neutralizing antibodies (block the penetration of the virus into the cell), and therefore they are excellent candidates for subunit vaccines, that is, they do not contain the entire pathogenic microorganism (inactivated or attenuated), but only a part of it – one or more surface immunogenic proteins. However, the unstable nature inherent in fusogens poses a serious obstacle to the development of an effective vaccine drug.
For vaccines, a "pre-fusion" fusogen is preferred: it is this conformation that contains important epitopes that are not present in the "post-fusion" conformation and induce the production of broadly cross- and highly neutralizing antibodies within a strong immune response. Traditional approaches of recombinant expression of viral fusion proteins usually lead to premature trigger effects and a conformational shift towards the "post-fusion" structure.
The technology has already been tested during the creation of chimeric polypeptides that mimic the conformations of fusogens "before the fusion" of influenza viruses, respiratory syncytial, HIV, measles and Ebola. For example, in the case of an anti-influenza vaccine, promising effects were demonstrated in animal models in vivo : a strong neutralizing immune response, broad cross-activity of antibodies to heterologous strains, high thermal stability without loss of antigenicity after 2 weeks of storage at a temperature of 37 ° C.
Novavax: virus-like nanovaccines
The biotech company Novavax Inc from Maryland (USA) has identified a new candidate vaccine NVX-CoV2373 against coronavirus and plans to start clinical trials in mid-May. She will use her own adjuvant Matrix-M in combination with the vaccine- NVX-CoV2373 to enhance the immune response. The company expects to receive preliminary data on immunogenicity and safety in July. NVX-CoV2373 is a recombinant vaccine based on nanoparticles. CEPI, which supports many vaccine developers, allocated $4 million to Novavax in March for research.
According to the results of animal studies, it can be concluded that the experimental vaccine from Novavax induces the production of specific antibodies against the thorn-shaped protein of the coronavirus. Theoretically, these antibodies prevent the virus from entering the cell. It is planned to recruit about 130 healthy volunteers for the phase I clinical trial.
Novavax develops various vaccines based on the technology of recombinant nanoparticles – particles containing antigens, which, due to their size comparable to those of cellular components, easily penetrate into the cells of the body through natural mechanisms of endocytosis. The pharmaceutical industry is working on many types of vaccine nanoparticles, including polymer, inorganic, liposomal, ISCOM, virus-like, self-assembling protein, emulsion.
Novavax has chosen vaccines based on virus-like particles (virus-like particles – VLP) – nanoparticles devoid of pathogenic nucleic acid and formed by self-assembly of biocompatible capsid proteins. In fact, we are talking about empty viral shells without any genomic DNA or RNA material responsible for replication. VLPs are an ideal nanovaccine system, since viral structures are used that are naturally optimized for interaction with the host body's immune system, but at the same time are devoid of infectious components. VLP vaccines have repeatedly proven their own safety and effectiveness in the face of vaccine preparations commercialized by other pharmaceutical companies, such as, for example, Recombivax HB (Recombivax HB) against viral hepatitis B, Gardasil (Gardasil) and Cervarix (Cervarix) against human papillomavirus, Hecolin (Hecolin) against viral hepatitis E.
Novavax is known for its developments of NanoFlu (NanoFlu) and ResVax (ResVax) – for the prevention of influenza virus and respiratory syncytial virus, respectively, which are in the final stages of clinical trials. Experimental vaccines contain viral fusion proteins and are supported by the proprietary saponin adjuvant Matrix-M, which reduces the dose of antigen and induces an additional immune response. Vaccines are produced on the cells of a lepidopteran insect – grass scoops (Spodoptera frugiperda) transfected with a baculovirus carrying the desired combination of genes.
Novavax is able to create a vaccine against SARS-CoV-2, ready for Phase I clinical trials. In the recent past, she designed a candidate vaccine against the pandemic H7N9 influenza virus 90 days after receiving its genetic sequence, and in 2017 it took the same amount of time to prepare an experimental vaccine against MERS-CoV.
Johnson & Johnson: The Ebola Experience
Johnson & Johnson will produce a vaccine against the new coronavirus infection COVID-19 at the enterprises of another company from the USA – Emergent BioSolutions Inc., intending to test 5 different vaccine candidates in parallel. Johnson & Johnson intends to enter into Johnson & Johnson global partnerships with other companies in order to increase the production of the candidate vaccine even before the end of clinical trials, which will begin in September 2020. Emergent will produce the substance for the vaccine and will provide Johnson & Johnson with production facilities for the production of the finished product. Under the terms of the mutual agreement, it will produce more than 1 billion doses of vaccine against coronavirus infection. The vaccine will be ready in early 2021, although individual samples may be delivered at the end of 2020.
Applied technological and production processes similar to those used for experimental vaccines against Ebola, Zika and HIV viruses. The chosen immunization strategy is similar to protection against fever Ebola, which is implemented by 2 heterologous vaccines according to the prime-boost scheme: first, a drug encoding viral antigens that primates the immune system is introduced, and then a recombinant protein that stimulates it.
Regarding the timing of the appearance of a ready-made vaccine against infection SARS-CoV-2, an American pharmaceutical giant, proceeds from the fact that during the Ebola outbreak it took about six months to design a vaccine drug, scale its release and start clinical trials, while the development of a vaccine against the Zika virus took almost a year. Johnson & Johnson hopes to optimize the processes by speeding them up by 2-3 months.
Oxford University: ChAdOx1 nCoV-19 vaccine
In the UK, the first clinical trials of a vaccine called ChAdOx1 will begin in May, and in March , preclinical animal tests were conducted at the Porton Down Laboratory under Salisbury. The ChAdOx1-nCoV-19 vaccine was created and tested by a combined group of scientists from Oxford University and the National Institutes of Health (NIH), led by Sarah Gilbert. The drug was developed following the example of another vaccine of this group of scientists against the Middle East respiratory syndrome (Middle East respiratory syndrome – MERS). The basis of the vaccine is a chimpanzee adenovirus with a small section of the genome "corrected" for SARS-CoV-2. Such a composition is injected into the body and causes its cells to produce the SARS-CoV-2 corona envelope protein. The immune system begins to produce antibodies to this antigen.
A single dose of the ChAdOx1-nCoV-19 vaccine in tests on macaques showed 100% effectiveness and protected monkeys from the development of coronavirus pneumonia and other lung damage after they were infected with SARS-CoV-2. 28 days before infection (so that antibodies could be produced in 4 weeks), 6 rhesus monkeys were injected intramuscularly with 2.5 • 1010 modified vaccine viral particles. This is half the dose for a person.
After that, the primates were infected with a "shock" dose of a real pathogen. A week later, it turned out that the vaccination protected them from lung infection – none of the test group developed pathology. The coronavirus antigen was also not found in the lung tissue.
It has been shown that the vaccine causes a strong immune response and protects the lungs of animals from damage and the development of pneumonia. All vaccinated animals produced neutralizing antibodies that prevent the virus from entering the cells, the scientists reported. Pneumonia did not develop in any of the 6 vaccinated macaques, while in the control group , inflammation developed in 2 out of 3 monkeys. In particular, vaccinated animals were found to have lower levels of viral RNA in lung tissue than those not vaccinated. These data allowed scientists to assume that the vaccine protected against the reproduction of the virus in the lungs. Vaccination with the drug did not cause a cytokine storm in rhesus monkeys - a destructive hyperreaction of immunity for the body.
A team of scientists has already launched the phase I clinical trial of ChAdOx1 nCoV-19, since April 23, volunteers have been vaccinated. As of May 13, more than 1,000 Britons have undergone the procedure. At the same time, mass production of 1 million doses of the vaccine began by September, without waiting for the results of clinical trials. As the scientists themselves explain, this is a necessary measure in a pandemic, which, in case of successful research results, will quickly provide people with a vaccine. They estimate their probable success at 80%.
At the University of Pittsburgh (University of Pittsburgh), USA, the first results of preclinical tests of a new SARS-CoV-2 coronavirus vaccine were obtained, the development of which was based on the experience gained when creating vaccines against SARS-CoV in 2003. and MERS-CoV in 2014. The prototype was developed on the basis of ready -made fragments of S-protein, which is necessary for the virus to overcome the immune response and penetrate into the human cell. Virologists have applied a new method of delivering the vaccine into the body – a patch with 400 tiny needles that deliver the vaccine into the body and then dissolve. In the near future, scientists plan to start clinical trials of the vaccine on volunteers. Johnson & Johnson, Arcturus Therapeutics and Inovio are also developing vaccines against COVID-19 in the United States Pharmaceuticals.
Russia
Russia wants to develop a vaccine on its own, and mainly by state scientific institutions. This, in fact, resembles the concept of import substitution – that is, a bet on the creation of domestic products, and not the purchase of imported ones. At the same time, the main financial burden is borne by the state. In Russia, the coronavirus vaccine 8 research centers are being developed.
State Scientific Center "Vector", Novosibirsk
The State Scientific Center of Virology and Biotechnology "Vector" of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being has developed 13 variants of vaccine prototypes based on 6 technological platforms: both on the basis of widely used recombinant viral vectors of influenza, measles, vesicular stomatitis, and on the basis of synthetic vaccine technologies, – mRNA-vaccines, peptide and subunit vaccines. The choice of technological platforms was based on the accumulated experience in creating vaccines against particularly dangerous viruses, among them:
- a peptide vaccine on a platform previously used to create a vaccine against the Ebola virus;
- subunit vaccine;
- live vector vaccine based on measles virus;
- recombinant intranasal vaccine based on influenza A virus;
- vector vaccine based on vesicular stomatitis virus;
- mRNA is a vaccine.
Currently, studies are being conducted on laboratory animals – mice, rabbits, ferrets and lower primates – in order to determine a promising prototype of the vaccine by April 30.
According to the Director General of Vector Rinat Maksyutov: "We propose to conduct preclinical studies of the effectiveness and safety of vaccines in a minimum volume until June 22 and with 3 vaccines to go to phase I of clinical trials on June 29 for a total of 180 volunteers."
Vector has already recruited volunteers. The studies will be conducted in 3 stages: safety testing, dose selection and studies in the focus of infection. The Vector employees themselves and some of their relatives became the first volunteers in the study of their vaccines. Coronavirus, as a particularly dangerous infection, is studied in a special building, where participants are vaccinated and kept for a day under the supervision of a doctor, the researcher and volunteer noted. There they constantly measure their body temperature and check the injection site. After that, the participants are sent home. Nevertheless, regular doctor's examinations and tests continue. Also, volunteers should monitor their own health and record changes.
The development of vaccines is taking place in record time, and by August–September 2020 they should appear for mass use in people, starting with critical groups of the population, primarily medical personnel. The second wave of coronavirus infection is predicted in Russia in October–December, and therefore domestic manufacturers are in a hurry to produce the first batches of the vaccine by this time. Vaccination will not be necessary for those people who have a high antibody titer detected by the ELISA method .
Federal Medical and Biological Agency (FMBA)
Another 7 prototypes of the vaccine are undergoing preclinical studies at the FMBA. Their results are planned to be received in June, and the second stage will be completed by the III quarter of this year. Stage I of clinical trials will take 5 months, stage II and III - another 15. However, in case of emergency, a ready-made vaccine can be obtained after 11 months. The FMBA has developed 7 prototypes of a vaccine against coronavirus. 2 FMBA centers are working on the development of vaccines, and a ready-to-use vaccine is expected to be received in 10-11 months. Moreover, in order to increase efficiency , the agency decided to switch to a three-shift work schedule. The developed vaccines were assembled genetically engineered "from recombinant proteins, each of which has epitopes, sites of binding to the virus." The vaccine is based on recombinant proteins that have binding centers with the virus. 3 types of recombinant proteins have already been created. Now scientists are analyzing them to identify the most effective binding centers with virus particles that increase the activity of the vaccine to the greatest extent.
"BIOCAD"
2 more vaccines are listed on the account of the company "BIOCAD", 3 prototypes of vaccines are assembled on the following 2 platforms:
- live viral vector vaccine based on attenuated influenza virus (jointly with the Institute of Experimental Medicine);
- mRNA encapsulated in liposomes, constructed on the basis of developments in the creation of mRNA-oncovaccines.
Preclinical animal studies were conducted until the end of April. The start of clinical trials of the vaccine is planned for May–June. Another development of "BIOCAD" is a vaccine based on adenovirus systems, in which the mechanism of virus replication has been completely removed.
Lomonosov Moscow State University (MSU)
The vaccine, which is offered by scientists of the Department of Virology of Moscow State University, is spherical particles from a plant virus that is not contagious to humans – a tobacco mosaic, which scientists have pasted with a surface spike protein S, which is visible on the virion from SARS-CoV-2 in the form of a crown and becomes like two drops of water similar to the pathogen itself. As a result, the human immune system responds to a specific "crown" and learns to fight the coronavirus without the virus itself.
According to scientists, the developed method will ensure a low cost of drugs, since it does not require the use of a weakened or killed pathogen, as well as expensive culture media. The cost of obtaining such spherical particles is low, since most viruses accumulate in the infected plant in large quantities, and the process of their isolation is simple and takes 2-3 days. Most of the time can be spent on creating genetic constructs and obtaining recombinant antigen proteins.
However, the most important point is that proteins from other coronaviruses, in particular SARS and MERS, can be attached to the surface of spherical particles. This is an approach that could provide protection against both past and future coronaviruses, which can manifest at any time and in the case of mutations SARS-CoV-2 based on the developed platform, it is easy to release an updated vaccine for the current strain of the virus in a short time.
Earlier, MSU successfully conducted preclinical studies of a rubella vaccine based on spherical plant viruses, which is completely safe, including for women of reproductive age and people with immunodeficiency.
St. Petersburg virologists from the Institute of Experimental Medicine are developing a universal vaccine against all types of coronavirus based on a live influenza vaccine. In the event of an epidemic, it can be quickly transformed into a vaccine against any type of coronavirus by embedding a gene of a certain serotype. The drug has successfully passed preclinical studies. It is planned to produce it in the form of a nasal spray.
Petrovax Pharmaceutical Company, one of the largest Russian manufacturers of influenza vaccines, is developing its own version of the vaccine . The company offers its adjuvant technology (with a complex of substances to enhance the immune response) to create a vaccine against coronavirus COVID-19 in In Russia and abroad, and is currently negotiating with several partners.
At the Institute of Fundamental Medicine and Biology Kazan Federal University creates individual proteins based on the digitized genome of the virus, from which the future gene vaccine is assembled. By reading information from these proteins, the body will form an immune response. The new method significantly reduces the time and cost of development.
The list of Russian manufacturers is completed by a vaccine in the form of recombinant protein, nanoparticles (based on S-protein and other epitopes), created in Scientific Research Institute of Vaccines and Serums (St. Petersburg).
In Russia, 9 COVID-19 vaccines have been developed, which are still in the category of promising and they have already been approved by WHO (among the world's developments, WHO has approved 83 vaccines). Minister of Health of the Russian Federation Mikhail Murashko said that the first drugs for vaccination against the new coronavirus may appear in Russia is closer to the end of July, and second -tier manufacturers will be able to provide a valid vaccine by the end of August. " We will live normally only after we start mass vaccination. Humanity has become vaccine–dependent because society and the politicians it chooses cannot allow people to die from infectious diseases," he said.
Sorrento Therapeutics and Celularity: Stem Cell Therapy
The American companies Sorrento Therapeutics and Celularity from New Jersey have engaged in testing the suitability of stem cells for the treatment and prevention of the new coronavirus infection COVID-19. We are talking about CYNK-001 cell therapy based on cryopreserved allogeneic natural killers (NK-cells) obtained from hematopoietic stem cells of the postpartum human placenta.
NK cells, being one of the types of cytotoxic lymphocytes and being an essential component of the innate nonspecific immune system, perform the same task for it as cytotoxic T cells for the adaptive immune system. NK cells, as well as cytotoxic T-cells provide rapid responses to virus infection of human cells and respond to the formation of tumors.
Blood plasma with neutralizing antibodies
Treatment with blood plasma of patients who have had COVID-19 is currently one of the promising ways to combat coronavirus pneumonia, since there is still no vaccine and effective medicines.
Transfusion of blood plasma with antibodies from the recovered person can create acquired passive immunity in the patient, helping him to fight infection. At the same time, only those people who recovered 2-3 weeks before blood donation will be able to become donors. They will have to donate 600 ml of plasma each. Already in a number of countries, blood banks have begun to be created, collecting material from people who have been ill with COVID-19. After the FDA officially approved the technique of plasma transfusion with antibodies to SARS-CoV-2, the New York Blood Center announced the widespread involvement of recovered patients to help the sick.
But the best results from the use of plasma will be obtained only if it is used in the so-called proactive mode, that is, when there are signs of infection that threaten serious pulmonary complications and, in particular, getting on the ventilator.
In addition, patients with COVID infection may develop disseminated intravascular coagulation syndrome, and then the main treatment method is replacement therapy with freshly frozen plasma, even if it does not contain antibodies to SARS-CoV-2 and heparin in therapeutic doses.
Humanity has known for a long time, more than 120 years, that plasma transfusion treatment can be effective. This was how patients were treated during the Spanish flu pandemic, during the swine flu, the H1N1 epidemic in 2008-2009, and even earlier, patients with diphtheria and bacterial diseases. With the development of vaccinations and antibiotics , plasma transfusion has faded into the background, but in recent years it has been used again in the fight against new diseases.
If the patient has not just antibodies in his blood, but antibodies neutralizing the virus, then it is possible to transfuse blood plasma (serum) to a patient or a person at risk. But we just need to remember that at the same time it is possible to "pour" some viral or other infection. Therefore , it is practically more correct to use purified preparations of total antibodies from the blood of those who have been ill.
Only 30% of those who have been ill have antibodies that neutralize the virus. This means that blood plasma to neutralize the coronavirus can not be taken from all recovered patients. The virus is very tricky. It is not for nothing that it is so large – the largest of the RNA-containing viruses known today. Part of the coronavirus genome is aimed at constantly deceiving the immune system so that the body produces dummy antibodies that cannot neutralize SARS-CoV-2.
Yes, it is artificially possible to make and develop neutralizing antibodies – this would become a highly science-intensive medicine, although quite expensive. But here we must understand that with successful vaccination , not only neutralizing antibodies are formed in us, but also lymphocytes that produce these antibodies. They provide immunological memory and protection for many years. And antibodies from transfused plasma have a limited lifetime in the body, and this circumstance reduces the prospects of such an approach for prevention.
Concentrates of purified antibodies
Regeneron Pharmaceuticals: antibody-based cocktail
American pharmaceutical company Regeneron Pharmaceuticals Inc. announced the identification of hundreds of antibodies capable of fighting the coronavirus and preventing its spread. Their clinical trials are planned to be conducted in early summer of this year. Back in 2015, the company managed to create a cocktail that halved the death rate from Ebola. And on March 17, she announced that she had determined the composition of a cocktail that could strangle the coronavirus. The pharmaceutical company has identified hundreds of coronavirus neutralizing antibodies that can potentially be used in the drug. It will be a kind of cocktail of antibodies.
Biotechnologists intend to choose 2 of the most powerful antibodies from the identified antibodies and, by mixing them, create a "cocktail" for the treatment of coronavirus. If his clinical trials are successful, the company will be able to release 200,000 doses of the new drug by the end of the summer. Regeneron is considered to be the creator of the most effective antibodies in the pharmaceutical industry, it has proven its ability to innovate and enjoys high investor confidence.
A spokeswoman for Regeneron, Alexandra Bowie, said that the new "cocktail", whose clinical trials are scheduled for the summer, can be used in combination with other vaccines currently under development. "A lot of different options are being tested at the same time these days," she said. "Over time, it will become clear which combination of medicines and vaccines is most effective."
Regeneron works closely with the US Department of Health in its work. In addition, to increase the intensity of future production, the company has established cooperation with the Federal Agency for Biomedical Research and units of the Ministry of Defense.
In addition to creating a "cocktail", Regeneron, together with Sanofi, is testing an existing drug called Kevzara (sarilumab) to combat coronavirus. This remedy is intended for patients with rheumatoid arthritis, but experts suggest that the antibodies contained in it may also be effective when trying to suppress viruses. The drug is also a monoclonal antibody specific to a specific receptor – interleukin-6, which causes inflammation. Sarilumab can block the function of this receptor, which means that inflammation can be controlled and stopped, so that the patient will not need artificial ventilation.
As a drug for the treatment of coronavirus infection, sarilumab is currently undergoing phase II and III clinical trials.
Sorrento Therapeutics: STI-1499 monoclonal antibody removes SARS-CoV-2 from the body in 4 days
Scientists from the California biopharmaceutical company Sorrento Therapeutics announced that the antibody STI-1499 can 100% suppress SARS-CoV-2 and quickly, in 4 days, remove it from the human body. In their opinion, this guaranteed treatment can be available much faster than a vaccine.
Scientists have analyzed billions of antibodies and identified hundreds of candidates that can bind to the spike protein of the SARS-CoV-2 virus to prevent infection of cells. The antibodies they detected showed neutralizing activity against SARS-CoV-2 and 1 of them were the most promising. As the first experiments showed, the antibody STI-1499 completely suppressed the activity of the virus at a very low dose, it acts by "enveloping" the virus to remove it from the body.
Founder and CEO of Sorrento Therapeutics Henry Gee told Fox News: "The cure is already there. There is a solution that works 100%." STI-1499 can become an independent treatment for COVID-19 or be used in a cocktail with others. We also identified about a dozen more antibodies that can block spike proteins from attaching to the ACE2 enzyme, through which SARS-CoV-2 usually penetrates into healthy cells. STI-1499 can be used as a prophylaxis, since it has no side effects," the director explained.
The company is ready to produce up to 200 thousand doses per month, but first permission must be obtained from the FDA regulator. The introduction of antibodies will form a person 's passive immunity to SARS-CoV-2 and he may stop being afraid of infection.
Vir Biotechnology: Natural antibodies
Vir Biotechnology, using proprietary biotechnology CellClone, on Humabs BioMed devices designed for screening and selection of highly effective natural antibodies that are isolated from Memory B-cells and plasma cells of recovering patients, created a concentrate of natural antibodies. The principle is simple: in some cases , completely unique antibodies with the highest therapeutic effectiveness are synthesized in the body of patients. They just need to be cleaned and concentrated.
These antibodies were identified in patients who recovered after infection with SARS-CoV or MERS-CoV. Some antibodies are able to neutralize zoonotic coronaviruses, and therefore it is possible that they will be useful in the case of SARS-CoV-2 and other similar infections. The task of isolating new antibodies specific to the Wuhan coronavirus has also been set. In addition, Vir intends to perform CRISPR screening of the viral genome to find out the exact receptor of the host cell, through which SARS-CoV-2 infects the body.
The advantage of the Vir approach is that we are not talking about artificial monoclonal antibodies, but completely natural ones collected by the immune system itself, which means that, firstly, they are stable in blood serum and, secondly, they are less likely to cross-react with host tissues. Such antibodies can be used both to treat a viral infection and to prevent infection. Unlike vaccines, which take time to trigger a protective immune response, antibodies initiate the latter almost instantly. Protection, however, will not be so long in time, but Vir is ready to extend it by introducing appropriate mutations in the Fc fragment of antibodies.
AbCellera Biologics: therapeutic monoclonal antibodies
Canadian AbCellera Biologics is trying to quickly not only to discover, but also to perform a clinical test of a therapeutic monoclonal antibody against the Chinese coronavirus.
The basic technological principle of AbCellera is based on a microfluidic platform that turns to tiny analyzers for screening antibodies from individual B cells of any living being. The analyzers are configured to search for specific therapeutic properties – depending on the target disease or application area. The platform has a large bandwidth, can carry out screening.
WuXi Biologics
China's WuXi Biologics, a major contract manufacturer of biological medicines, has created a research group of hundreds of specialists in order to develop a variety of neutralizing antibodies against COVID-19 coronavirus infection. In the near future, the first batch of antibodies ready for preclinical toxicological examination and clinical trials on humans will be released. It is planned that in 4-5 months it will be possible to pass all the proper stages of verification in order to submit a dossier for registration – instead of the traditional ones 12-18 months.
Israel Institute of Biological Research (Israel Institute for Biological Research – IIBR)
The Israeli Defense Minister said that scientists have identified antibodies that actively attack the coronavirus in the body of infected people. They can probably be used to create a vaccine, writes New York Times.
"A monoclonal neutralizing antibody developed at the Israeli Institute of Biological Research can neutralize the coronavirus that causes disease inside the bodies of carriers," Defense Minister Naftali Bennett said.
The reported antibody is detectable monoclonal, meaning that it was obtained from a single recovered cell and thus potentially more effective for treatment.
Non-COVID-19 vaccines that stimulate nonspecific innate immunity May protect against COVID-19
BCG. US epidemiologists have found a link between the BCG tuberculosis vaccine and a decrease in the incidence of coronavirus. The results of the study are published on the medRxiv portal.
It is noted that in countries where vaccination is not accepted BCG, most affected by COVID-19.
In Western countries, such as the USA, Italy, Spain, Belgium, the Netherlands, BCG was literally abandoned because of the "good life" - the incidence of tuberculosis there is extremely low, although still 100 years ago, this disease was one of the main causes of death. In these countries, the incidence of coronavirus was 4 times higher than the global average. Especially the mortality rates have repeatedly exceeded the data in the post-Soviet states, where BCG vaccinations are mandatory.
Scientists have come to the conclusion that vaccination can become one of the main tools in the fight against coronavirus. The data on the possible effect of BCG vaccinations are very interesting, but indirect. Therefore , direct experiments have now been launched, the results of which will have to wait several months.
The Netherlands and Australia are trying to confirm this fact. In Australia, about 4 thousand doctors took part in testing a tuberculosis vaccine as one of the methods of countering coronavirus infection, and in the Netherlands , 1,000 medical workers were involved in 8 Dutch hospitals, who will also receive either a BCG vaccine or a placebo.
According to scientists, BCG vaccination in a certain way stimulates nonspecific innate immunity and, above all, local immune protection of the lungs and reduces the likelihood of severe forms of coronavirus infection.
The BCG vaccine, in addition to the prevention of tuberculosis, is used in oncology and, above all, in the immuno-therapeutic treatment of cancer bladder, protects against infectious Buruli ulcers.
Live Oral Polio vaccineKonstantin Chumakov, Deputy Director of Science at the FDA's Vaccine Division, Professor at George Washington University
Washington University), and the University of Maryland (University of Maryland), participates in the study of the safety and efficacy of vaccines that receive approval for admission to the market in the United States. The scientist also proposed his own approach to the prevention of a new coronavirus infection – to use a live oral polio vaccine for this as a means of protection against coronavirus. Clinical trials will soon begin in New York and Baltimore on the basis of the Institute of Human Virology at the Medical School of Maryland (University of Maryland School of Medicine) under the direction of Robert Gallo, one of the discoverers of the human immunodeficiency virus, awarded The Nobel Prize for this discovery.
Clinical studies conducted back in 1970 with the participation of more than 60 thousand people, it was shown that the polio vaccine protects against influenza better than the influenza vaccine. Their results were forgotten, but they were updated due to the coronavirus problem .
A live vaccine has a non-specific protective effect: when children were vaccinated with this vaccine, the safe vaccine virus displaced all other viruses that can usually be detected in healthy children.
The Ukrainian phenomenon of low morbidity and mortality from COVID-19 can possibly be explained by mass vaccinations with the OPV polio vaccine 4-5 years ago, when cases of polio appeared in Ukraine, including those caused by the vaccine strain in the west of the country. Although vaccinations were given mainly to children, a live weakened vaccine strain could be transmitted to the adult population and lead to latent immunization and activation of innate immunity.
PneumovaccineIn the context of the spread of COVID-19, the Ministry of Health of the Federal Republic of Germany recommended that all people over the age of 60 be vaccinated against pneumococcal infection: this will not protect against coronavirus, but it will help avoid a number of complications with pneumonia, including deaths.
After the 65-year-old Chancellor Angel Merkel publicly joined the pneumovaccine vaccination in Germany during the week there was a shortage of it.
The pneumovaccine is not effective against coronavirus, but if a person develops pneumonia as a result of COVID-19 , then a pneumococcal bacterial infection will not join it, which means there will be fewer complications. In older people, severe pneumonia is often caused by pneumococcus and proceeds very hard.
When a person suffers a coronavirus infection, then on the 14th-20th days from the onset of the disease, a pronounced immunodeficiency condition develops. This is included in the scenario of a viral infection, the protective properties of the respiratory system are sharply weakened, and a favorable situation arises for pneumococcus, which inhabits the oropharyngeal region. As a result, it descends into the lower respiratory tract. And the anti-pneumococcal vaccine is exactly the remedy that can protect in such a situation.
Conclusion
The vaccine is considered the only means for the final victory over COVID-19, in its absence, no return to normal life of the pre-quarantine level is expected. Hundreds of laboratories around the world joined the race for the championship. The most advanced scientific laboratories promise to hand over the first working batches of vaccines in the period from August to the end of 2020. And such vaccines, which will be ready in late autumn, are expected to be 8. Specialists will have to choose 2-3 for large-scale research and application. Governments of all countries and WHO believe that vaccination should be free of charge, since the production of a coronavirus vaccine is not a business, it is an important social function of states and international organizations.
US experts predict that, most likely, the first vaccine will be Chinese, but perhaps it will not be as high-quality as the ones following it, which will come out with a 1-2-month lag. Such an advance of Chinese specialists is due to the fact that they just joined the work 2 months earlier. It is also clear that China and Russia will use their vaccines inside their countries, at least at the first crucial stage. Another thing is that it is unclear by what time it will be possible to cover the entire population of the planet with vaccination. Most likely, this will happen before the end of 2021. It is from this period that it can be expected that the SARS-CoV-2 virus will disappear, as it happened with the SARS SARS virus, or SARS-CoV-2 will enter the category of seasonal pathogens of acute respiratory diseases.
There are two dangers in creating an effective vaccine – mutational variability of the new coronavirus, which some virologists suggest, and an antibody-dependent increase in sensitivity to SARS-CoV-2, which cast doubt on the success of obtaining an effective vaccine.
For example, due to the unusually high variability of HIV , the whole world has been trying to develop a vaccine for AIDS prevention for 35 years - and so far to no avail. Although "HIV pills" have already been developed to effectively support health.
However, sequencing of hundreds of SARS-CoV-2 virus isolates in various laboratories around the world, which is carried out on an ongoing basis, confirmed the low variability of this virus. Analysis of all genomes shows a very high level of identity, more than 99.9%. All this confirms that concerns about the rapid variability of the SARS-CoV-2 virus are premature.
An antibody-dependent increase in sensitivity to coronavirus, despite reasonable doubts, has not yet been traced for SARS-CoV-2, vaccine prototypes show their protective effectiveness. This unusual phenomenon (antibody-dependent increase in infection) was identified more than half a century ago and lies in the fact that sometimes in the presence of specific antibodies, the virus begins to behave even more aggressively and infection only intensifies. This phenomenon is very rare, but quite well studied. And the most unpleasant thing is that both predecessors and close relatives of the new coronavirus behaved in a very similar way – SARS (2003) and MERS (2012).
The SARS-CoV-2 pandemic could have been prevented if big Pharma had not lost interest in the previous SARS and MERS coronaviruses – because they disappeared from the face of the Earth. The work on the creation of vaccines and medicines that had begun was suspended halfway through.
The only way to treat COVID-19 at the current stage is the victory of immunity over infection. With the available means, a person can only alleviate the symptoms while his body is fighting the disease itself.
Understanding the principles of immunity will help to better resolve the issue of lifting quarantine measures, as doctors will understand who is not at risk of infection, and who will not become a carrier of infection.
Any product that strengthens the immune system can be useful in the fight against coronavirus. The choice of such a product depends entirely on the preferences of each individual. The main thing is to lead a healthy lifestyle, not to plunge yourself into stress, sleep 7-8 hours, eat right with sufficient protein intake, do not overload yourself with high–calorie and overcooked food, do not forget about vegetables and fruits and vitamins A, C, E, D and zinc, which are key for good immune function. Flavonoids, beta-glucans, and tilorone adequately stimulate the immune system.
The emergence of the AIDS epidemic in the 1980s in the United States had a huge impact on the development of immunology and related technologies around the world. The current COVID-19 pandemic will undoubtedly attract the attention of governments, scientists, businesses, and ordinary citizens of different countries to immunology and the importance of immunological research. It is possible that the views on immunity will not be radically revised, but I would like to hope that funding, the quality of education and the level of fundamental science in this important area will improve, and that there will be fewer non-working drugs with the prefix immuno-in pharmacies.
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