The second phase of the Russian HIV vaccine begins

Our vaccine against our HIV

Nadezhda Markina, Newspaper.Roo

About the features of the Russian DNA vaccine against HIV, about past and future clinical trials "Gazeta.Ru" was told by its developers.

The vaccine will save 20 billion rublesIn a few years, we can expect that a domestic vaccine against the human immunodeficiency virus (HIV) will appear in Russia.

If she successfully passes clinical trials. Unless some bureaucratic or interdepartmental barriers stand in the way of its creation, as it often happens. And if the state gives money to complete its tests. Now the creators of the vaccine – Doctor of Biological Sciences Andrey Kozlov, director of the Biomedical Center in St. Petersburg, and his colleagues are ready to conduct the second phase of clinical trials of the vaccine. It will begin in June as part of the federal target program "Pharma 2020".

We are talking about a therapeutic vaccine, not a preventive one. This means that it is used not to avoid contracting AIDS, but to treat people already infected with HIV.

This is one of three domestic vaccines mentioned by the Minister of Health Veronika Skvortsova. The other two, created at the Institute of Immunology in Moscow and at the Vector Center for Virology and Biotechnology in Novosibirsk, have passed the first phase of clinical trials, but have not yet received money for the second. So the registration, which the minister said, is still far away.

The number of HIV-infected people in Russia is, according to various sources, from 950 thousand to 1.3 million people. In order not to die from AIDS, they take medications for life that suppress the reproduction of the virus – this is called antiretroviral therapy. You can live with therapy, but you can't stop it, because medications crush the virus, keep it in check, but they don't completely remove it from the body. In addition, addiction develops to medications and the treatment regimen has to be changed. Finally, the treatment of HIV-infected people is very expensive. Nationwide, antiretroviral therapy costs 20 billion rubles annually, although this is not enough and 40 billion rubles are needed today.

A therapeutic vaccine is a medicine that fights the virus, increasing the capabilities of the body's immune system. But it is the immune cells (T-lymphocytes) that become the main target for HIV, and when infected, their number decreases. The vaccine restores the number of immune cells and sets them against the virus, because it itself contains the components of the virus.

Vaccination can be combined with antiviral therapy, reducing the dose of drugs. Theoretically, it can allow a person to do without medication at all, that is, it can cure him completely. However, this is such a great goal that experts strive for, but so far they are talking about it very carefully. If you manage to reduce the dose of medications, it's already good.

Its own vaccine against its own virusThe Russian DNA vaccine contains four viral genes, so its conditional name is DNA-4.

Moreover, as explained by "Newspaper.En" Andrey Kozlov, these are the four main genes of the virus and they cover all the antigenic regions of the viral genome, to which an immune response occurs.

Most importantly, the vaccine is made on the basis of our Russian HIV – this is HIV-1 serotype A. "We are lucky in that the virus circulating in the Russian population is little changed," explains Kozlov, "its variability is within 5% compared to the 20% variability of HIV in some other populations". This means that the domestic vaccine will be intended for the treatment of Russian patients.

Scientists have cloned a viral genome, isolated genes from it and inserted them into a plasmid – the ring bacterial DNA of E. coli. "We did everything with our own hands," emphasizes Andrey Kozlov. – Usually in our clinical practice it happens that half is stolen abroad. Nothing has been stolen from us."

During the production of the vaccine, and it takes place at the Research Institute of Especially Pure Biological Products in St. Petersburg, these plasmids multiply and are purified from accompanying proteins and foreign DNA. At the end – mandatory quality control to get exactly what you need.

From animals to patientsAs Andrey Kozlov says, the vaccine has passed "all imaginable preclinical studies", which showed that it belongs to the 5th class on the toxicity scale, that is, it is completely non-toxic.

In experimental animals, the vaccine caused cellular immunity – the immunity created by T cells. Then the human trials began.

The first phase of clinical trials, in which 21 healthy volunteers participated, was conducted by specialists in 2008-2010. It was confirmed that the vaccine is well tolerated, does not cause side effects and in 100% of cases causes cellular immunity in humans. To show this, many immunological studies were conducted on volunteers.

The second phase of clinical trials will involve 60 HIV-infected patients who are receiving antiretroviral therapy. And they will be conducted by seven medical institutions: in Moscow, Volgograd, Kazan, Kaluga, Lipetsk, Izhevsk, Smolensk. Patients will be divided into three groups. Two groups will receive the DNA vaccine in two different doses, and the third group will receive a placebo (without the vaccine). Doctors will monitor three groups of subjects for six months, monitor their condition, measure the content of viruses in the blood and conduct all kinds of immunological tests.

"Since this is the first use of the vaccine in HIV patients, the first task is to test safety on patients," says Natalia Vostokova, director of the contract research organization IFARMA, which organizes clinical trials. – We vaccinate them against the background of antiretroviral therapy. We need to make sure that the vaccine triggers an immune response. We will monitor general health indicators, a general blood test, an ECG and immune indicators."

Experts have preliminary data that the vaccine removes a temporary increase in the virus in the blood that occurs during treatment. This, they explain, may be a sign of drug resistance. According to Kozlov, if these data are confirmed, the vaccine can be included in the protocol of antiviral therapy.

Race against the virusThe vaccine may appear on the market within four to six years.

According to Kozlov, it depends on a lot of circumstances, but first of all, no matter how banal it sounds, on money. The Ministry of Health is proud to report on domestic vaccines, but something does not seek to finance this work. As well as the Federal Medical and Biological Agency of Russia (FMBA).

At the first stage of vaccine development, researchers received money from the Ministry of Education and Science, then from Rospotrebnadzor, and the most expensive part – the second phase of clinical trials – became possible thanks to the federal program "Pharma 2020" announced by the Ministry of Industry and Trade. "However, very little money is allocated for it," experts complain. - 50 million rubles. – this is actually a short supply."

If it were not for financial problems, the other two HIV vaccines would also have started the second phase. Andrey Kozlov's words about competitors' products do not feel any rivalry: when asked what will happen if they prove effective, the scientist answers: "Well, then they can be used in combination, and this will only strengthen their effect."

In general, he emphasizes, a lot of clinical trials should be conducted in the country at the same time, and only in this mode will new drugs appear.

By the way, under the same Pharma 2020 program, the second phase of clinical trials of another Russian product is now starting - this is a drug against HIV, created, as the Newspaper wrote.Ru", in the company "Viriom" of the center for chemical diversity "Himrar".

As she told the Newspaper.En" representative of "Himrara" Elena Surina, in the first phase the drug was tested in Thailand and a decrease in the virus in the blood of patients after a short application was noted. Now permission has been obtained for testing in Russia on 90 patients for a year. The effect of the Russian drug will be compared with the gold standard of HIV infection treatment.

Russian scientists began working on medicines and then vaccines against HIV at the same time as American scientists, in the 1990s, says Andrey Kozlov. But the United States, unlike our country, spends billions of dollars on these developments. However, the Americans have not yet had a working vaccine either — "the mountain gave birth to a mouse."

And our specialists need to work quickly, because Russian HIV, which was stable for the time being, has already begun to mutate: a new recombinant variety has been discovered in Novosibirsk and Tomsk. And if it spreads, it will be necessary to create a new vaccine for more conservative areas of the virus.

In principle, the Russian vaccine is also suitable for prevention, for protection against HIV infection. But it's almost impossible to check it. "Trials of a preventive vaccine for effectiveness will require a cohort of several thousand people with an infection rate of several percent per year to statistically prove that it removes infection. And even if you find such a cohort of subjects among people with drug addiction, it will cost several tens of millions of dollars," says Kozlov.

"In general, what is the AIDS epidemic? – the scientist sums up. – This is an epidemiological war of nature against us. And we have to defend ourselves from it."

Portal "Eternal youth" http://vechnayamolodost.ru09.06.2014