This page has been robot translated, sorry for typos if any. Original content here.

Superantela nearly defeated hiv

Human broad spectrum antibodies against HIV reduce the concentration of the virus in the blood to an indiscernible level. Science observes this effect for the first time - however, so far only in experiments on monkeys.

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

But even antiretroviral cocktails only help to transfer the disease from the acute to the chronic phase. Such therapy can not do anything with a virus that is floating 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, the usual anti-HIV therapy theoretically allows you to get rid of the virus, but only under special conditions, and such cases, alas, are rare.)

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


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

However, our immunity is still able to cope with such a diversity of the virus, creating a broad-spectrum antibodies. The fact that immunity can produce immunoglobulins that recognize more than 90% of HIV varieties was discovered by scientists in 2010, and this discovery, of course, inspired everyone with hope that AIDS is about to fall. But over time, it turned out that such antibodies rarely appear and after a huge period of time, moreover, only in response to a real infection — that is, to provoke their synthesis with a vaccine from a killed pathogen will not work.

Nevertheless, scientists continued to work with similar antibodies. And not so long ago, it was possible to detect universal antibodies, which appear much earlier and look simpler than those that have been observed before - true, and their universality turned out to be lower. But is it necessary to force the immune system itself to produce such antibodies? Experiments have shown two research groups - from the Medical Center deacon Beth Israel and the National Institute of Allergy and Infectious Diseases (both - the United States) - broad-spectrum immunoglobulins, simply introduced into the blood, effectively reduce HIV levels.

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


Immediately it should be said that the groups of Dana Baruch (Dan Barouch) and Malcolm Martin (Malcolm Martin) experimented with monkeys: the Rhesus were infected with a hybrid monkey-human HIV, which bred in macaques, but looked like a human virus. The weapons against it were broad-spectrum antibodies obtained from AIDS patients.

Dan Baruch and his colleagues used a cocktail of three types of antibodies, and, as the researchers in Nature say, during the week the virus level dropped so much that it could not be detected! A similar result was also when, instead of a mixture of immunoglobulins, only one of them was used. After the level of such antibodies in the blood began to decrease, the concentration of the virus rose again, but in some monkeys it still remained indiscernably low even without introducing additional portions of antibodies.

In another work done by Malcolm Martin and his colleagues (and published in the same journal), we are talking about the same thing, only here the researchers used other types of antibodies against HIV. And again, the concentration of the virus fell in monkeys for seven days before the indistinguishable (once again: indistinguishable!) Level and remained so for 56 days, until the antibodies themselves began to disappear. Then everything depended on how much the monkeys had from the monkeys initially: if there was little, then after the disappearance of the antibodies, the virus remained under the control of the animals' own immunity, but if there was a lot of it initially, then the level started 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 to be resistant to the antibodies administered. (However, there was one exception: when in the second study only one antibody was injected, and the experiment was a macaque with 3 years of cohabitation with the virus, it had a resistant viral strain.)

In both cases, scientists did not treat the virus with human antibodies for too long, as they feared that the monkey's immune system would begin to resent the alien immune proteins, and perhaps this was 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 be clarified 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 reduced so much (alas, previous experiments with antibodies that were performed on humans and mice had rather inexpressive results).

What's next? The cost of antibodies is much higher than antiretroviral drugs, and 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 the antibodies are also added to substances that prevent the reproduction of the virus in the cell.

Prepared by materials National Institute of Allergy and Infectious Diseases and Deaconite medical center Beth Israel .