Will monoclonal antibodies help in the treatment of AIDS?

Superantibodies have almost defeated HIV

Kirill Stasevich, CompulentaAIDS 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 entering the cell, it uses the enzyme revertase (reverse transcriptase) to make a copy of DNA on its own RNA template. Then, with this DNA, the cell's own proteins begin to stamp viral RNA. If, say, the reverse transcriptase of the virus is suppressed, then it will not be able to reproduce.

But even cocktails of antiretroviral drugs only help to transfer the disease from the acute phase to the chronic one. Such therapy can do nothing with a virus that floats in the blood or is in a cell in a dormant state. Therefore, researchers are looking for a way to get rid of the virus itself, and not just to 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 rare.)

When it comes to completely expelling HIV, everyone agrees that there is no better tool to find antibodies here. On the one hand, everything is simple here: it is enough to find immunoglobulins that would recognize the protein of the viral envelope, bind to it and signal to the immune killer cells that this complex needs to be destroyed. The problem, however, is that HIV has enormous 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 immune system is still able to cope with such a variety of viruses, creating broad-spectrum antibodies. The fact that the immune system can produce immunoglobulins that recognize more than 90% of HIV varieties, scientists discovered in 2010, and this discovery, of course, gave everyone hope that AIDS was about to fall. But over time it turned out that such antibodies occur rarely and after a huge period of time, moreover, exclusively in response to a real infection – that is, it will not work to provoke their synthesis 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, although their universality turned out to be lower. But is it necessary to force the immune system itself to produce such antibodies? As the experiments of two research groups from the Beth Israel Deaconess Medical Center and the National Institute of Allergy and Infectious Diseases (both USA) have shown, broad–spectrum immunoglobulins simply injected into the blood effectively lower the level of HIV.

HIV between an epithelial cell (bottom) and a lymphocyte (top) (photo by Visuals Unlimited / Corbis).It should be said right away that the groups of Dan Baruch and Malcolm Martin experimented with monkeys: Rhesus were infected with hybrid monkey-human HIV, which multiplied in macaques, but looked like a human virus.

Broad-spectrum antibodies obtained from AIDS patients served as a weapon against it.

Dan Baruch and his colleagues used a cocktail of three types of antibodies, and, as the researchers write in Nature (Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys), within a week the virus level dropped so much that it could not be detected! A similar result was when only one type of immunoglobulin was used instead of a mixture of immunoglobulins. After the content of such antibodies in the blood began to decrease, the concentration of the virus rose again, but 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 (Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia), we are talking about about the same thing, only here the researchers used other types of antibodies against HIV. And again, the concentration of the virus dropped in macaques for seven days to an indistinguishable (once again: indistinguishable!) level and remained so for 56 days, until the antibodies themselves began to disappear. Then everything depended on how much virus the monkeys had initially: if there was little, then after the disappearance of the antibodies, the virus remained under the control of the animals' own immunity, if there was a lot of it initially, 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 no resistance to the injected antibodies appeared. (However, there was one exception: when only one antibody was injected in the second study, and the subject was a macaque with 3 years of experience of cohabiting with the virus, she had 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 start to resent foreign immune proteins, and perhaps this was the reason that in most cases the virus recovered. That is, it is not yet clear whether this effect can be made "long-lasting". All this will be clarified only after clinical trials; as for the results described above, the enthusiasm of the researchers can be understood: for the first time in a living organism, it was possible to reduce the level of viremia so much (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 that of antiretroviral drugs, and it is more difficult to handle them. But the authors of the works believe that such antibodies need to be combined with conventional anti-HIV drugs: this will reduce the cost of treatment, and most likely increase its effectiveness – if you also add substances to the antibodies that prevent the virus from multiplying in the cell.

Prepared based on the materials of the National Institute of Allergy and Infectious Diseases (HIV Antibody Infusions Show Promise for Treating SHIV-Infected Monkeys) and the Medical Center of Deaconess Beth Israel (Monoclonal Antibodies Show Promise As Effective HIV Therapy).

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