Monkeys cured of immunodeficiency
Gene therapy has defeated the most invulnerable form of "monkey" HIV
American molecular biologists have created a vaccine capable of destroying all traces of the most dangerous form of the monkey immunodeficiency virus, and have successfully tested it in action on macaques. The results of their experiments and the prospects for creating a similar HIV vaccine were revealed in the journal Science Translational Medicine (Gardner et al., AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges).
"We managed to solve two main problems of all existing HIV vaccines – the short duration of protection and its narrow profile. No other therapy can protect the body from the effects of the two viruses we worked with," said Michael Farzan from the Scripps Research Institute in Jupiter (in a press release, Viral HIV vaccine gives durable protection against 'death star' strain – VM).
Infection with HIV and many other dangerous viruses usually proceeds in two stages. At first, the virus actively multiplies in the body of a new victim, which leads to the activation of immunity and the appearance of a malaise similar in symptoms to the flu. When the body begins to fight the virus, the infection goes into a chronic stage, gradually depleting the immune system.
Today, HIV patients can live for decades thanks to the use of antiretroviral drugs – substances that suppress various stages of virus replication in the cells of the body. Since they often have strong side effects, doctors are often forced to stop taking them for several weeks.
When they stop taking them, HIV "gets out of the trenches" and begins to intensively copy itself, often returning to the initial scale of infection in three or two weeks. In recent years, scientists have been actively trying to find drugs or antibodies that would help avoid such a "counterattack" of the virus, or would allow the virus to be "kicked out" of cells.
Biologists place special hopes on gene therapy, which, in theory, allows you to find all traces of the virus in infected cells and destroy them. The first successful experiment of this kind was completed quite recently – in early July, geneticists from the United States announced that they had managed to cure two "humanized" mice using the CRISPR/Cas9 genomic editor.
The problem, as Farzan and his colleagues note, is that the immune system of an infected person, mouse or monkey often interferes with the work of gene therapy, destroying "therapeutic" viral particles and suppressing the synthesis of antibodies or other molecules that are necessary to fight HIV. In addition, almost all its varieties are aimed at combating specific subtypes of the virus, which sharply limits their effectiveness.
American molecular geneticists have overcome both problems by radically changing the strategy of fighting the virus. They did not "cut out" it or force the immune system to produce antibodies to HIV, but created a kind of "Trojan", a bait for viral particles.
As Farzan explains, it is a cross between a broad-spectrum antibody, which patients begin to produce a few years after infection, and one of the main "targets" for HIV, the CD4 molecule.
Similar protein chains are found in large numbers on the surface of T cells and other components of immunity, and the immunodeficiency virus uses these outgrowths to penetrate them and infect them.
Scientists decided to take advantage of this by creating a shortened version of this receptor, eCD4-Ig, which connects with virus particles before they have time to join immune cells, blocks their disclosure and marks them for destruction.
After testing the performance of these molecules in a test tube, the scientists embedded instructions for their assembly into a retrovirus capable of penetrating the muscle cells of macaques and other primates and forcing them to produce large amounts of Trojan CD4. These molecules are released into the bloodstream, where they meet HIV and neutralize it.
After treating four rhesus monkeys with this vaccine, scientists tried to infect them with the "usual" variety of the monkey immunodeficiency virus, as well as its most dangerous variety, SIVmac239. This virus has evolved together with macaques for many centuries, thanks to which it is ideally adapted for life in their body and it is almost impossible to suppress it by any existing methods.
As it turned out, the "Trojan" eCD4-Ig molecules completely coped with this task – all monkeys were protected from infection, despite the fact that scientists injected very large doses of the virus into their bodies. About six months later, the scientists repeated the experiment, and only one monkey became a victim of the virus due to the fact that its muscles began to produce fewer baits.
Interestingly, further observations showed that SIVmac239 tried to adapt to fight the "Trojan" copies of the receptors by changing its structure in two ways. In both cases, he managed to do this, significantly impairing his ability to infect cells and multiply rapidly.
Now scientists are developing new versions of the vaccine that would be devoid of these shortcomings, which, they hope, will open the way for the creation of similar viruses adapted to fight the human form of HIV.
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