05 June 2018

Record holder among vaccines

Doctors have created a vaccine that protects against 30% of HIV strains

RIA News

American virologists have created the first experimental vaccine that creates immunity to about a third of HIV strains, and tested its work on mice and macaques, according to an article published in the journal Nature Medicine (Xu et al., Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1).

"My colleagues found an Achilles' heel in the structure of the virus, which allowed them to create a new and potentially very strong vaccine. This study will be the first step towards creating a safe and truly reliable method of protection against HIV," said Anthony Fauci, director of the National Institutes for the Study of Allergies and Infections in Bethesda, USA (in a press release NIH HIV vaccine elicits antibodies in animals that neutralize dozens of HIV strains ). The immunodeficiency virus penetrates into human cells using a set of several proteins on the surface of its shell. Their structure and the structure of the hydrocarbon "shield" protecting them changes with each new generation of HIV, which forces the immune system to produce a new set of antibodies. In the overwhelming majority of cases, the virus becomes the winner in this "arms race", and this same feature prevents scientists from creating a vaccine or vaccination against HIV.

As immunologists explain, 3-4 years after HIV infection, the human immune system often begins to synthesize so-called broad-spectrum antibodies (bNAbs), capable of neutralizing several varieties of the virus at once. This does not help the body much, since by this time the virus will already have time to penetrate deeply into all the tissues of the body and go into the chronic stage.

Peter Kwong from the National Institutes for Allergy and Infection Research and his colleagues have been studying the structure of these antibodies for many years, trying to understand which parts of HIV they cling to and how the human body can be forced to reproduce them without coming into contact with a "live" virus.

To do this, due to the variable structure of HIV and the lack of a complete understanding of how it penetrates into human cells, is not so easy – in most cases, scientists have managed to create a vaccine that gives immunity to several varieties of the virus.

The situation changed two years ago when Kwon and his colleagues discovered an extremely unusual antibody, named N123-VRC34, in the blood of one of the carriers of the virus. This molecule clings not to the virus envelope, but to the so–called "fusion peptide" - a special gp41 protein that "glues" the cell membrane with an HIV particle and allows viral RNA to penetrate inside it.

The structure of gp41, as scientists note, almost does not change compared to the rest of the virus, as it plays a critical role in its life cycle. This prompted biologists to think that such an antibody could be used as a base for an HIV vaccine.

After treating several HIV particles with these antibodies, the scientists froze them, enlightened them with a particle accelerator and found out which part of gp41 N123-VRC34 "clings" to. Having received this data, biologists have grown several copies of this site, collected so that they irritate the immune system as much as possible.

antibodies-HIV.jpg

The location of the fusion peptide epitope (red) on the HIV glycoprotein spike (green), which protrudes from the viral membrane (gray). The figure also shows how neutralizing antibodies (yellow) bind to the fusion peptide (from the NIH-VM press release).

The most effective versions of this protein, as shown by experiments on mice and monkeys, made them immune to infection with about 70 of the 208 existing HIV strains today, which remains a record for vaccines so far.

Now scientists continue to modify the structure of proteins, hoping to increase the effectiveness of vaccination, and are looking for new antibodies that interact with gp41. The first version of the vaccine will begin clinical trials, scientists hope, in the second half of next year.

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