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Superantibodies nearly defeated HIV

Broad-spectrum human antibodies against HIV reduce the concentration of the virus in the blood to an indistinguishable level. This is the first time science has observed such an effect — though so far only in experiments on monkeys.

So far, AIDS patients have only one hope - antiretroviral therapy, which is based on drugs that prevent the spread of HIV. The genome of this virus is written in RNA, so after it enters the cell, using the reverse transcriptase enzyme, it makes a copy of the DNA on its own RNA template. Then, with this DNA, the cell’s own proteins begin to stamp viral RNA. If, say, suppress the work of reverse transcriptase of the virus, then he will not be able to multiply.

But even cocktails of antiretroviral drugs only help to transfer the disease from the acute phase to the chronic one. Such therapy cannot do anything with a virus that floats in the blood or is in a cell in a sleeping state. Therefore, researchers are looking for a way to get rid of the virus itself, and not just suppress its ability to reproduce. (By the way, conventional anti-HIV therapy theoretically allows you to get rid of the virus, but only under special conditions, and such cases, alas, are isolated.)

ВИЧ и человеческий лимфоцит (фото Callista Images)
HIV and a human lymphocyte (Callista Images photo)


When it comes to completely expelling HIV, everyone agrees that it is better to find no tool for antibodies here. On the one hand, everything is simple: it is enough to find immunoglobulins that recognize the viral envelope protein, contact them and signal to the killer immune cells that this complex needs to be destroyed. The problem, however, is that HIV has tremendous variability, and antibodies usually only catch a certain fraction of the viral particles, because the same protein is endowed with a number of differences due to which the antibodies cannot see it.

However, our immunity is still able to cope with such a variety of viruses, creating antibodies with a wide spectrum of action. The fact that immunity can produce immunoglobulins that recognize more than 90% of HIV species, scientists discovered in 2010, and this discovery, of course, inspired everyone with hope that AIDS was about to fall. But over time, it turned out that such antibodies rarely occur and after a huge period of time, besides exclusively in response to a real infection - that is, they could not be provoked with a vaccine from a killed pathogen.

Nevertheless, scientists continued to work with similar antibodies. And not so long ago, it was possible to detect universal antibodies that appear much earlier and look simpler than those that were observed before - however, their universality turned out to be lower. But is it necessary to force the immune system itself to produce such antibodies? As shown by the experiments of two research groups - from the Deaconess Beth Israel Medical Center and the National Institute of Allergy and Infectious Diseases (both from the USA) - broad-spectrum immunoglobulins, simply injected into the bloodstream, effectively lower the level of HIV.

ВИЧ между эпителиальной клеткой (снизу) и лимфоцитом (сверху) (фото Visuals Unlimited / Corbis).
HIV between the epithelial cell (bottom) and the lymphocyte (top) (photo Visuals Unlimited / Corbis).


It’s worth saying right away that the groups Dan Barouch and Malcolm Martin experimented with monkeys: Rhesus was infected with a hybrid monkey-human HIV that bred in macaques, but looked like a human virus. The weapons against him were broad-spectrum antibodies received from patients with AIDS.

Dan Baruch and his colleagues used a cocktail of three types of antibodies, and, according to researchers in Nature, within a week the level of the virus fell so much that it could not be detected! A similar result was when instead of a mixture of immunoglobulins, only one species was used. After the content of such antibodies in the blood began to decrease, the concentration of the virus rose again, however, in some monkeys, it still remained indistinguishably low even without the introduction of additional portions of antibodies.

In another work, performed by Malcolm Martin and his colleagues (and published in the same journal), this is about the same, only here the researchers used different types of antibodies against HIV. Once again, the concentration of the virus fell in macaques within seven days to an indistinguishable (once again: indistinguishable!) Level and remained so for 56 days until the antibodies themselves began to disappear. Further, everything depended on how much virus the monkeys had initially: if it is small, then after the disappearance of the antibodies, the virus remained under the control of the animal’s own immunity, but if it was originally there was a lot, then the level began to grow.

At the same time, as the researchers emphasize, the virus disappeared both from the blood and from other tissues, and it did not appear any resistance to the introduced antibodies. (True, there was one exception: when only one antibody was introduced in the second study, and the subject was a macaque with 3 years of experience cohabiting with the virus, it developed a stable viral strain.)

In both cases, scientists did not treat the virus with human antibodies for too long, because they were afraid that the monkeys immune system would begin to resent foreign immune proteins, and this was probably the reason that in most cases the virus was restored. That is, it is not yet clear whether this effect can be made “long-playing”. All this will become clear only after clinical trials; as for the results described above, the inspiration of the researchers can be understood: for the first time in a living organism, the level of viremia was so reduced (alas, previous experiments with antibodies that were put on humans and mice had very inexpressive results).

What's next? The cost of antibodies is much higher than antiretroviral drugs, and it’s more difficult to handle them. But the authors of the works believe that such antibodies should be combined with conventional anti-HIV drugs: this will reduce the cost of treatment, and, most likely, increase its effectiveness - if substances are added to the antibodies that prevent the virus from multiplying in the cell.

Prepared by materials National Institute of Allergy and Infectious Diseases and Deaconess Beth Israel Medical Center .