An international team of scientists has found a way to overcome the main obstacle that has stalled the development of an HIV vaccine: the inability to generate long-lived immune cells that stop viral infection.
A study conducted in Thailand and published back in 2009 found that an experimental HIV vaccine reduced human infection rates by 31%. This made it possible to cautiously assume that in the near future it will be possible to obtain a vaccine with significantly more high level efficiency. However, the main obstacle to creating such a vaccine is that the immune response obtained with its help was very short-lived. A team of scientists from the UK, France, USA and the Netherlands, led by Professor Jonathan Heeney from the Laboratory of Viral Zoonotics at the University of Cambridge, managed to find out the reason for this obstacle, and find a potential way to overcome it .
How HIV works
Once a virus enters a cell, its sole purpose is to create multiple copies of itself to infect other cells, spreading throughout the body. HIV is famous for the fact that the gp140 protein on its outer shell targets CD4 receptors on the surface of lymphocytes - T-helper cells, the main regulators of the immune system. They produce important signals for other types immune cells: B cells, which produce antibodies, and killer T cells, which kill virus-infected cells.
By selectively targeting CD4 receptors on T helper cells, HIV disables the command and control center of the immune system, thereby preventing it from effectively responding to infection. The virus doesn't even need to get inside the T cells and destroy them: it simply causes them to paralyze.
The main “weapon” of HIV has become a component of the vaccine
Human immunodeficiency virus envelope proteins gp140 may become a key component of vaccines to protect against HIV infection. The body's immune system finds this protein and generates antibodies that coat the surface of the virus and thereby prevent it from attacking T helper cells. If the effect of the vaccine lasts long enough, then with the help of T helper cells the human body should learn to independently produce antibodies that neutralize most strains of HIV and thereby be able to protect people from infection.
Previous studies have shown that vaccination using the gp140 outer protein of the virus triggers B cells that produce antibodies to the virus, but only for a short period of time. This time was too short to receive sufficient quantity antibodies that protect against HIV infection for a long period.
Professor Jonathan Heaney concluded that binding of the gp140 protein to CD4 receptors on T helper cells is likely the cause of this problem. He suggested that by preventing gp140 from binding to the CD4 receptor, the vaccine could be made to work longer. Two studies published in the Journal of Virology proved that this approach works, providing the desired immune response that lasts for more than a year.
“For a vaccine to work, its effects need to be long-lasting,” says Professor Haney. “Vaccination every 6 months is too impractical. We wanted to develop a vaccine that creates long-lived cells that produce antibodies. And we found a way to do it."
A small key to a big riddle
Scientists have discovered that adding a tiny specific protein to the gp140 protein blocks its binding to the CD4 receptor and therefore prevents T helper cell paralysis at early stages immune reaction. This small patch was just one of several strategies to modify the gp140 protein for an HIV vaccine. It was developed by a team led by Susan Barnett.
This little key, added to a vaccine containing the gp140 protein, is much better at stimulating long-lasting B cell responses, increasing their ability to recognize and produce different viral envelope contours. specific antibodies. This new approach will allow the development of an HIV vaccine in the foreseeable future, which gives the immune system enough time for B cells to create the necessary protective antibodies.
“The B cells needed to buy time to produce highly effective neutralizing antibodies. In previous studies, the B cell responses were so short that they disappeared before they could complete all the changes needed to create the 'silver bullets' for the HIV virus,” adds Professor Haney. “Our discovery will significantly improve B cell responses to the HIV vaccine. We hope that our research will bring the creation of an effective, long-lasting HIV vaccine much closer.” The team of scientists expects to receive additional funding in the near future in order to begin testing the effect of the vaccine on humans.
The creation of a vaccine against HIV has been announced more than once
This is not the first time that scientists have announced that they are close to creating a vaccine against HIV. However, until 2013, all statements turned out to be premature: all the vaccines, on the creation of which huge amounts of money and time were spent, were not only ineffective, but in some cases even increased the likelihood of contracting HIV.
In 2013, scientists from Duke University School of Medicine managed to get closer to creating a universal vaccine against HIV (/mednovosti/news/2013/04/04/hivvaccine/), for the first time not only tracking the process of generation, maturation and interaction of neutralizing antibodies with the virus, but and by identifying the conditions under which their production becomes possible.
That same year, scientists announced that they had succeeded in ridding 50% of experimental rhesus monkeys of the immunodeficiency virus.
In 2014, Novosibirsk virologists announced their readiness to begin the second phase of clinical trials of the experimental HIV vaccine they developed, CombiHIVvac. At the end of 2015, scientists from St. Petersburg tested the DNA-4 vaccine on volunteers infected with HIV. Author of the vaccine development, director of the St. Petersburg Biomedical Center, doctor biological sciences, Professor Andrei Petrovich KOZLOV argued that with the successful completion of clinical trials, the DNA-4 vaccine could enter the market as early as 2020.
World media reported the successful testing of an HIV vaccine. What does this mean, the editors of the Attic looked into it, and we are sharing it with you.
Researchers from the USA and Germany reported in the journal Nature the results of clinical trials of the 3BNC117 antibody. These antibodies are protein molecules that literally stick to viruses at the site they use to fuse with the infected cell. As a result, the virus remains intact, but no longer poses any harm. Antibodies were isolated from the blood of an HIV-positive donor back in 2011, and scientists immediately realized their potential: at the end of 2013, after successful experiments on mice, clinical trials in public.
All clinical trials are usually divided into three phases. In the first, the vaccine or drug is usually first administered in minimal doses to healthy volunteers to ensure the drug's safety; then, in a small group of patients, the effectiveness and safety are tested at the dosage that will be used in practice. The second phase involves larger number patients, and testing of effectiveness is of paramount importance, and in the third phase new drug compared with existing analogues during tests on large quantities sick.
IN in this case scientists and doctors reported the successful completion of the first phase, so it is too early to draw clear conclusions about the effectiveness and safety. Although the results are very encouraging: one dose of antibodies was enough for at least 28 days - this is how long a significant decrease in the number of viruses was observed in the blood of patients.
Let us emphasize: it was precisely the decrease, the viruses did not completely disappear. Therefore, it is not yet possible to talk about a medicine that can solve the HIV problem at its roots.
Medicines and vaccines
The drug developed by scientists is not the only vaccine against HIV. In particular, there is a vaccine called RV144, which is supposed to act as preventive vaccination. Its clinical trials have so far shown conflicting results, and research in this direction continues further. Several people are trying to create vaccines. different ways and for different purposes - both to prevent HIV infection and to prevent AIDS.
It must be emphasized that HIV-positive status and AIDS are significantly different concepts. HIV-positive status means that the body has the human immunodeficiency virus, HIV. And AIDS is a disease that develops when viruses weaken the immune system so much that it can no longer cope with those pathogenic microorganisms which can usually be contained.
The modern approach to the fight against AIDS is to prevent its occurrence - to protect against infection. And if infection occurs, the virus is prevented from multiplying with special medications. Antiviral drugs can delay AIDS for a very long time: with timely initiation of therapy, HIV-positive people live as long as everyone else.
Another thing is that the drugs currently used against HIV are expensive (the conclusion about life expectancy was made in developed countries) and have a number of side effects. Antibodies, apparently, will not be cheap, but it makes sense to talk about this only after the end of the third phase of trials. The already mentioned RV144 vaccine showed encouraging results during trials in the first phase, but then doctors found out that the drug did not provide the protection that was originally expected.
Three myths about HIV
First, now rare: the virus is allegedly transmitted by everyday means, through towels or dishes. It is not true. Children's horror stories about infected needles in seats or sandboxes are also unconvincing: the virus outside the human body quickly dies when it dries out. You can become infected with hepatitis at home, but HIV cannot.
Second, quite common: infection allegedly threatens only those who use injection drugs (due to a syringe shared by several people) and homosexual men (due to anal sex). This is not true, although both of these modes of transmission of the virus do make a significant contribution to the epidemic. Currently most of infections occur through heterosexual contact.
Third, equally popular: condoms supposedly do not protect against HIV, since latex has pores. Latex is indeed porous, but condoms are made from many layers of latex, and the microstructure of the material resembles a thick layer of cheese rather than a sieve. As a result of the application of many layers, condoms perfectly retain water, the molecules of which are much smaller than the virus! And latex is not the only material for these contraceptives. A condom does not provide a 100% guarantee due to the non-zero probability of rupture or simply incorrect use, but it greatly reduces the risks.
AIDS - Acquired Immune Deficiency Syndrome - (English AIDS) is a disease that affects the body's defense system. It is caused by HIV, the human immunodeficiency virus. After infection to the human body Even a simple cold becomes dangerous. In AIDS, it can cause serious complications. In Russia, as of December 31, 2015, 1,006,388 cases of the disease were officially registered. Of these, 27,564 people left last year alone. This explains why the AIDS vaccine is so needed.
Important: Medicines against HIV, as well as tested and approved vaccines, are this moment(at the beginning of 2016) no. Although many countries have already announced that the drug has been developed and is being tested. So far, patients receive only maintenance therapy to prolong life. While the virus mutates, it adapts to the drugs used.
Specifics of the disease
HIV infects CD4 lymphocytes, and these are the same cells that destroy the causative agents of all other diseases. As the number of “guards” decreases, the body’s level of protection decreases significantly. As a result, a person remains practically defenseless against infections. of various etiologies, tumors, including malignant ones, also feel at ease.
If, according to the results of a blood test, the number of CD4 lymphocytes does not exceed 200, the disease has progressed to the AIDS stage. It takes up to 10 years from HIV infection to the development of AIDS.
Attention: The disease is not detected immediately after infection. It takes 6 to 12 weeks for the body to produce antibodies. In some cases, the fact of infection is confirmed only 6 months after the infection occurred.
Feature of HIV that prevents development effective medicine against it is that the virus is integrated into the genome of the host cell, which begins to multiply with a “broken” genome, spreading its influence. Accordingly, a cure is possible when it is possible to knock out (erase) this harmful information from the human genome.
There is a known case of the “Berlin patient,” a man with HIV who was diagnosed with leukemia. A transplant was required to treat cancer bone marrow. The patient was matched with a donor who lacked CCR5 receptors. In their absence, HIV cannot attach to the genome. People with this mutation do not get the disease. After transplantation, the diagnosis of immunodeficiency in the “Berlin patient” was no longer confirmed.
Russia
By November 2015, according to the statement of the head of the Federal Medical and Biological Agency V. Uiba, funding for the development of the vaccine was suspended. But domestic scientists have created three experimental drugs. All of them passed the 1st stage of clinical trials, i.e. they were tested on healthy people. The second stage is the use of the drug on HIV-positive patients, when the drug must show what specific strain it works against.
The results of clinical trials are currently being assessed. After this, it is planned to continue the development of these projects.
USA
Representatives of the Californian Scripps Research Institute said that they had created a powerful and universal agent that can be used as part of an unconventional vaccine designed to prevent HIV. More than 10 American research institutes are involved in the development.
The main goal of the creators is to achieve stable remission in victims of HIV.
An experimental drug obtained by American scientists, eCD4-Ig is capable of blocking strains of HIV-1, HIV-2 and SIV until they are completely neutralized. The protein binds to the shell of the virus, which antibodies are unable to do.
Thanks to the drug, it was possible to prevent infection in experimental monkeys for a full 8 months after the vaccine was administered to them. This vaccine against HIV was able to block even a 16-fold dose of the virus. The primate immune system did not react in any way to the introduction of eCD4-Ig, which is explained by the fact that this protein is to a certain extent similar to parts of the cells of the monkeys themselves.
The drug is based on the knowledge that the CCR5 coreceptor has special changes in the region required by HIV to communicate with the host cell. The drug obtained as a result of scientific experiments is capable of forming a strong bond simultaneously with two areas of the surface of HIV, thus depriving it of the chance of penetrating the host cells. eCD4-Ig successfully imitates the receptors “needed” by the virus, preventing it from “escaping.”
To deliver the drug directly to tissue, the technology of using an adeno-associated virus was used. This is a relatively safe viral culture that does not cause any diseases.
eCD4-Ig problem: The result of a drug whose effects the body will continue to experience long years, unpredictable. Human clinical trials were planned to begin in 2015.
Finland
Back in 2001, biochemists from Finland began testing a vaccine whose action is based on a gene mutation. Patients were injected with immunodeficiency virus DNA plasmids, which were supposed to stimulate the production of an anti-HIV substance.
The drug was not tested because it was not released to the market.
By the same principle, reverse classical technology creating a vaccine, some pharmaceutical companies are trying to create vaccines against cancer.
Norway
Also at the end of 2015, biotech company Bionor Pharma from Norway reported successful trials of their version of an anti-HIV drug. The technology is based on stimulation of latent cells into which the virus has invaded, with the simultaneous administration of medicine. The combination of the drug Romdepsin and the Vacc-4x vaccine was able to reduce the reservoirs of latent HIV cells by 40%.
Summary
It will take about 15 years before a drug that has reached the trial stage reaches the market. There are already about 10 vaccine options in the world. All successfully pass the second stage of testing. But they cannot overcome the third, when the effectiveness of anti-HIV drugs must be proven positive results samples from thousands of volunteer patients. In the next 5-7 years similar drug will not appear.
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HIV infection has become one of the most important problems in modern world. There have been 71 million cases since the outbreak began in 1980. The human immunodeficiency virus (HIV) is most widespread in South Africa, where the number of patients is about 7 million people. According to statistics, there are about 1 million HIV-infected patients in Russia. Of them antiviral treatment only 110 thousand people receive it. The number of patients increases by 10% annually.
Scientists from leading countries around the world are working to create a vaccine against AIDS. When will there be a vaccine for HIV? Why is there still no vaccine for AIDS? Let's try to understand these difficult issues.
Western developments of vaccines against HIV infection
Decision on state program to create a vaccine against HIV infection was adopted in the USA and Russia in 1997. Available worldwide different ways creating a drug for HIV.
What developments are currently underway? News on the HIV vaccine in the world is as follows.
All these studies have not yet reached the stage of vaccine production. However, trials are actively carried out on volunteers and give good results. But clinical stage requires many years of research. The production of a vaccine against HIV is only a matter of time. Even after successful research, scientists achieve long-term effectiveness in most people. And this requires a lot of time.
Russian development of AIDS vaccines
Russia also has the prospect of creating HIV vaccines. Currently, testing has not yet reached the full-scale stage. In St. Petersburg, on the basis of the biomedical center, together with the Federal State Unitary Enterprise “State. Research Institute of OCB" created the DNA-4 vaccine against HIV. In addition to it, 2 more HIV vaccines were created in Novosibirsk and Moscow.
The development of the St. Petersburg vaccine is led by Professor Doctor of Biological Sciences A. Kozlov. He is also the director of the biomedical center. Scientists Polytechnic University under the leadership of A. Kozlov, using funds from a won grant to study the immunodeficiency virus, they continue to develop a vaccine against HIV infection. To date, they have conducted 2 stages of clinical trials on volunteers. The third large-scale stage of the study is ahead. Once the trials are completed, the vaccine will be presented to everyone globally. The vaccine is planned for release in 2030.
First stage of clinical trials of DNA-4 vaccine
All three Russian vaccines have passed the first stage of testing. A study of the St. Petersburg preventive vaccine was conducted in 2010 on volunteers uninfected with HIV. The experiment included 21 people of both sexes. They were divided into 3 groups, in each of which the same dose of the vaccine was administered - 0.25, 0.5 or 1 ml.
Based on the results of the study, the following conclusions.
- The vaccine showed no side effects. It is safe and non-toxic.
- In response to the administration of the minimum dose of the drug, a 100% response of the immune system was obtained.
- The virus is detected in the blood immediately after infection, and not after several weeks. If treatment with specific drugs is started at this time, HIV infection does not develop. This information is important for healthcare workers after an accidental cut from a contaminated instrument.
- During the study, it was noticed that some people did not become infected after unprotected contact with HIV-infected people.
It was noted that infection did not occur after constant contact with one infected partner. According to scientists, these people had previously suffered from an infection similar to AIDS, as a result of which they developed cross-immunity. There is another version, according to which 5% of Europeans are genetically protected from the immunodeficiency virus.
Second stage of DNA-4 vaccine trials
The second phase of clinical trials of the St. Petersburg vaccine drug began in 2014 and was completed in 2015. A therapeutic version of the HIV vaccine was being tested, so AIDS patients were recruited for the experiment. Groups of volunteers formed AIDS treatment centers from 6 cities of Russia. The trials involved 54 HIV-infected volunteers who received specific antiviral drugs from 6 months to 2 years. The vaccine is designed to combat subtype A virus, common in Russia.
At this stage, randomized controlled trials were conducted in a double-blind manner. Sick volunteers were randomly divided into three groups. Members of one group were injected with 0.5 ml, and the second - 1 ml of the substance. The third group received a placebo - saline. Neither the subjects nor the doctors knew which group received how much vaccine. Only one of the scientists who conducted the experiment knew about this.
The test results showed the following preliminary conclusions.
- HIV-infected patients tolerate the vaccine well.
- A minimal dose produces an immune response.
- In infected people, viruses can be reduced to such an extent that they can be controlled the immune system person.
The name DNA-4 vaccine means that it contains 4 genomes of the virus. Although this genome coverage is sufficient, scientists are going further - they are developing a vaccine drug DNA-5.
Preliminary studies of the vaccine after two stages of the study allow us to conclude that it belongs to group 5 on the safety scale. There is no infectious agent in it, so the ampoules can be destroyed in the usual way. It induces immunity even after a minimal dose, so there is a possibility of reducing the amount of the administered substance.
What difficulties arise when creating an HIV vaccine?
Project leader Professor A. Kozlov reports on the difficulties that arise all over the world when trying to create a vaccine against HIV infection. The main problem is the excessively rapid mutation of the HIV virus. It has several dozen subtypes, within which great changes also occur.
In America and Africa, type B of the virus is common, and in Russia and Belarus - type A. Moreover, the virus, common in Russia, is characterized by mutation to a lesser extent than the American subtype B. But in general, subtype A has already shown a tendency to accelerate mutation. This means that over time it will be necessary to create new vaccines against HIV infection with different strains. This creates additional challenges in vaccine development.
There is another obstacle in creating vaccines - the individual's immune response to the vaccine. The uniqueness of the human body does not make it possible to predict how the vaccine drug will behave in each individual case. U different people the same substance does not cause the same type of reaction. But scientists are achieving average vaccine effectiveness.
In Russia, the stumbling block to creating an HIV vaccine is the lack of a federal program and proper funding. These and many other factors explain why there are still no vaccines against HIV.
Latest news on vaccine trials in Africa
Fresh news about the HIV vaccine comes from Africa. At the end of 2016 in 15 regions South Africa Large-scale trials of a new vaccine began. They cover about 6 thousand people aged 18 to 35 years. Participants were randomly assigned to 2 groups. Over the course of a year, volunteers in one group are given 5 injections of the vaccine drug, and the other group is given a placebo (saline solution) according to the same scheme. This ensures a controlled study. All vaccinated persons are sent to medical institutions to monitor and provide necessary assistance.
The research is tailored to the type of virus that is prevalent there. The tests are based on a substance that, after testing in Thailand in 2009, showed 31% effectiveness. National Institute infectious diseases The US, led by its director Anthony Fauci, has high hopes for new vaccine. The results of the study will be completed in 2020. Scientists believe that a vaccine, even with minimal effectiveness, can reduce the spread of infection. After all, clinical trials are taking place in countries where 1 thousand people become infected with the infection every day.
Cloned antibodies against HIV infection
Comforting news about HIV vaccination came from scientists in America and Germany. In 2015, an antibody-based vaccine was successfully tested at New York University. With their help, scientists were able to suppress the development of HIV infection.
The neutralizing antibody, code-named 3BNC117, is produced in the blood of only 1% of HIV-infected patients. In such people, when infected, the infection does not develop, but is cured. Scientists cloned this antibody and injected it into the blood of other patients. Neutralizing antibodies are able to stop the development of infection - they can protect against 195 of the 237 strains of the virus. In some volunteers, the concentration of the HIV virus decreased by 8 times. This inspired the experiment participants and scientists. But upon further research, it turned out that the vaccine did not produce any results in some of the subjects. In addition, the confrontation does not last long due to rapid viral mutation.
One of the authors of the project, Florian Klein, noted that the results are encouraging. Despite the fact that the effect is still short-lived, scientists plan to create another type of antibody that can be combined with the first. This will extend the effectiveness of the HIV vaccine by 1 year. The project will take a lot of time and will cost the patients a lot of money.
Another group of scientists led by Michel Nussenzweig in 2016 used antibodies in HIV-infected patients after they stopped taking antiretroviral drugs. The concentration of the virus in the blood remained at a low level 2 times longer than usual - the protection lasted 2 months.
Are HIV-infected people vaccinated?
In patients suffering from HIV infection, the immune system is weakened by this virus. Any vaccinations also weaken the body's defenses for some time. The question naturally arises: is it possible to get regular vaccinations for HIV infection? Not all vaccinations are dangerous for infected patients. Vaccines are divided into live and inactivated (killed or weakened). After administration of a live drug, a person suffers light form diseases, after which immunity is developed. This kind of vaccine poses a danger to HIV patients. But there is inactivated vaccines, after which a person does not get sick.
For those infected HIV people infection poses a much greater danger. A weakened immune system will not allow you to cope with it. Therefore, it is vital for infected people to be vaccinated against the following diseases.
- People are vaccinated against influenza before the seasonal epidemic begins.
- Vaccination against measles, rubella and mumps is given healthy people once in a lifetime. But in infected people this live vaccine They don’t always do it - check the level first immune status. Acceptable level must be at least 200 cells per 1 ml.
- Hepatitis vaccination is necessary for HIV-infected people. Vaccination against virus A protects a person for 20 years, against hepatitis B - for 10 years.
- Vaccination against pneumonia is necessary for people with HIV because they are susceptible to infection 100 times more often than healthy people. After all, in case of illness, the disease ends in death. The vaccine protects people for 5 years.
- Against diphtheria and tetanus after vaccination in childhood Revaccination is done once every 10 years. But for HIV-infected patients it is done under the control of the level of immunity.
Patients with HIV infection are vaccinated at the AIDS Center under the supervision of doctors. 2 weeks before vaccination, they are given a course of vitamin therapy to support immunity. Some vaccinations are mandatory for these patients.
Let us summarize and recall the main points about the development of a vaccine against the human immunodeficiency virus. All countries of the world are taking part in the development of a vaccine against HIV. Various ways to create a vaccine preparation are proposed. Research on three vaccines continues in Russia. Scientists in Germany and the USA have tested cloned antibodies against HIV. Large-scale trials of the vaccine are currently underway in Africa on 6 thousand volunteers. On the way to creating drugs, scientists encounter various problems associated with virus mutation and the immune response. Despite this, some vaccination success has already been achieved in 15 regions of South Africa. The research results will be known in 2020.
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