10 December 2021

Vaccination against HIV infection

Experimental HIV RNA vaccine successfully tested on animals

Sergey Vasiliev, Naked Science

Scientists from the American National Institute of Allergy and Infectious Diseases (NIAID) have successfully tested a new HIV RNA vaccine on animals. Macaques who received the drug showed an almost 80 percent lower risk of infection than unvaccinated ones. Paolo Lusso and his colleagues write about this in an article published in the latest issue of the journal Nature Medicine (Zhang et al., A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques).

The experimental vaccine was created with the participation of Moderna specialists and fundamentally works the same way as its RNA vaccine against the new coronavirus. The vaccine particles deliver matrix RNA molecules that encode the virus protein to the cells of the body. The cells at the injection site "automatically" begin to produce it, causing a reaction of the immune system. In the case of the HIV vaccine, two proteins important for this virus are used — Env and Gag.

Experiments on mice have shown that a couple of injections of the drug are sufficient for the appearance of neutralizing antibodies in them. The authors noted that, unlike many previous similar developments, their vaccine leads to the synthesis of Env protein in the body, which practically does not differ from the form in which it exists in the shell of a real virus. This makes the immune defense more reliable. Next, the scientists conducted experiments on macaques.

Several groups of animals received the first injection, and then, over the course of a year, a series of "booster" ones that contained the mRNA of Env and Gag proteins of different HIV strains. According to the researchers, this was supposed to stimulate the immune system to develop more "universal" antibodies. By attacking the most conservative, stable areas of the virus, they are able to protect against a wide range of its varieties.

No serious side effects were noticed after the injection. By the 58th week, all vaccinated animals had antibodies that "in vitro" successfully neutralized representatives of 12 HIV strains. In addition, macaques had a powerful response from T cells, showing that they had learned to recognize the virus for attack.

Starting from the 60th week, the animals were exposed to infection by weekly injection of a modified primate and human immunodeficiency virus (Simian-Human Immunodeficiency Virus, SHIV). Primates are not infected with HIV themselves, and for such studies, a kind of hybrid between a human virus and its close relative (SIV) affecting wild primates was obtained.

After the 13th week, two of the seven experimental macaques remained uninfected. In the rest, the infection began, but still noticeably later than it usually happens with unvaccinated animals — on average, at the eighth week, and not at the third. This shows that the immunity of such macaques coped with the attacks of the virus for a long time and lost far from immediately.

According to scientists, they plan to further refine their vaccine and test its effectiveness and safety again. If the experiments are so successful again, we can proceed to clinical trials on volunteers. Meanwhile, clinical trials of another HIV vaccine, HIVconsvX, have been underway in several African countries since the summer of 2020.

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