Gaining altitude
What we know about the Russian HIV vaccine
Polina Loseva, N+1
In early December, the head of Rospotrebnadzor, Anna Popova, spoke about the "high degree of readiness" of the Russian HIV vaccine. The other day, its developers confirmed to journalists that in the first phase of clinical trials, 100 percent of volunteers had antibodies to the virus. By the way, an article with their report was published back in 2016 (Karpenko et al., A combined HIV-1 vaccine based on artificial polyepitope immunogens: results of phase I clinical trials).
Let's see what can actually be said about the "height" of the readiness and effectiveness of this vaccine.
HIV is an eternal epidemic, the Achilles heel of the Ministry of Health around the world and the sore corn of virologists. None of the attempts to develop reliable protection against this virus has so far been successful. Modern medicine is also unable to finally cure the patient, except for one unconfirmed case and several patients who got rid of the virus along with their own blood cells. The most successful (if we can say so about the failed trial) of the HIV vaccines was 31.2 percent effective – this "height" has been held for 11 years.
Therefore, the best thing we can do today to counter the HIV epidemic is to test everyone at risk in time and provide them with medicines to prevent the virus from multiplying in the blood. But this task – the so–called "90-90-90" program - is not easy for all countries. And if, contrary to expectations, a vaccine could still be invented, it would significantly simplify our lives.
What kind of vaccine?
The vaccine that Popova was talking about (Kombivichvak) is being developed by the Novosibirsk Vector Center – the same one that is currently working on a vaccine against SARS-CoV-2. Moreover, he has been dealing with the problem of HIV for a long time – at least in 2011, the Center has already conducted the first phase of testing of its vaccine.
According to the mechanism of action, "Kombivichvak" refers to polyepitope vaccines. This is an artificial virus-like particle, that is, a protein "box" inside which there is a ring DNA with some viral genes. Such a design should arouse suspicion in two branches of immunity at once. B cells should react to surface proteins and start producing virus-specific antibodies. And DNA should get inside human cells and make them also collect several surface proteins of the virus – and introduce them to T-cells.
This technology itself is not new – polyepitope vaccines have been tested against HIV before, but they did not cause a significant immune response. However, a polyepitope vaccine should solve an important problem. The fact is that it is difficult to protect a person from HIV once and for all – the virus evolves very quickly and changes the structure of its surface proteins. That is why all attempts to make a vaccine have so far failed – while the body is getting used to a specific image of the virus, it is already being overtaken by a new one that has changed beyond recognition. At the same time, the rate of HIV mutation is orders of magnitude higher than that of the flu, from which we are vaccinated every year (precisely because the virus has time to change in a year so that the old "habits" of immunity lose their force).
A polyepitope vaccine should prepare the body for a meeting with several types of enemy at once. Proteins that "stick out" on the surface of virus-like particles in the vaccine combine fragments of several variants of viral proteins at once. And the DNA that it contains encodes, according to the developers, conservative sites – that is, those that should remain unchanged even in a mutating virus.
What is the result?
Many media outlets today released notes with headlines that "the Russian HIV vaccine is effective," or even "100% effective."
But the only thing we know today about the efficiency of "Kombivichvak" is the results of the first phase of its tests, published in 2016 in the journal "Bioorganic Chemistry".
The first thing that is checked during clinical trials of the vaccine is safety. In their article, the organizers of the experiment report that they did not notice any pathological changes in the volunteers, or even local reactions.
The second thing to measure is immunogenicity, that is, the ability to trigger an immune response directed against the desired virus. According to the authors of the work, all the volunteers had antibodies to at least one of the standard set of HIV proteins. In addition, 100 percent of the participants had HIV-specific T-lymphocytes, which, upon meeting with the virus, began to produce the antiviral protein interferon gamma.
Also, many found neutralizing antibodies – that is, those that do not just stick to the surface of the viral particle (this just does not stop the virus), but also prevent it from penetrating into the cell, preventing infection. Therefore, it can be assumed that the immune system of the majority of subjects reacted to the vaccination.
There is only one "but". Antibodies from the volunteers' blood neutralized different subtypes of the virus with different efficacy. Six months after vaccination, 71 percent of participants could "neutralize" the antibodies of variant A/392, and variant B/PV04 – only 29 percent. And a year after the injections, none of the subjects had these antibodies left in their blood.
Is it possible to rejoice already?
Of course, you can be happy – at least for the test participants who have received confirmation that their immune system is in order, and also – perhaps – some degree of protection against HIV.
But it is certainly too early to make claims that "the vaccine is effective".
The fact is that the results cited by Interfax above were obtained as a result of the first phase of clinical trials. Strictly speaking, even the safety and immunogenicity of the vaccine should be spoken with caution – only thirty people participated in the first phase (half received one injection, another half received two injections, and the researchers did not have a control group at all). And who knows how the vaccine will behave in a large sample among people of different genders, ages and with various concomitant diseases.
The second phase of testing started back in 2013 and should be completed in December 2021. 240 people are already taking part in it – but we do not yet know anything about the design of the experiment (for example, whether there is a placebo group in it and what substance plays its role), nor about the composition of the sample of volunteers. And to check the effectiveness, which, in fact, serves as a measure of the value of the vaccine, is the task of the third phase, which is out of the question so far.
Therefore, if you can't wait to stock up on the hope of an HIV vaccine, you can pay attention to two other vaccines that have been making their way through the third phase of trials for a long time – in the USA and South Africa. And if you want fresh and good news, you can be happy for Uganda: the third phase of clinical trials of two vaccines started there just a couple of days ago.
Portal "Eternal youth" http://vechnayamolodost.ru