02 November 2018

"Multibody" against influenza

Llamas helped scientists create a "nano-vaccination" against all types of flu

RIA News

The immunity of llamas helped geneticists from the United States to create nanoantibodies that neutralize almost all common strains of the influenza virus, including the famous "swine flu" H1N1. The results of their experiments on mice were presented in the journal Science (Laursen et al., Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin).

"It was extremely difficult to create or discover an antibody that would simultaneously act on influenza viruses from groups A and B that periodically infect humans. I have never seen an antibody that acts so strongly on so many viruses. We hope that our retroviral "vaccination" will protect a person from infection all season," said Ian Wilson from the Scripps Institute in La Jolla (USA).

Nature's Help

The so-called nanoantibodies are a fragment of an "ordinary" antibody containing only one randomly arranged "building block", from which their molecules are usually assembled. Thanks to this, nanoteles are much more compact and stable, and also better tolerate heating and aggressive chemical environments, including gastric acid and digestive enzymes.

Similar antibodies are not found in the body of humans and almost all other animals, but recently (in 1993, Naturally occurring antibodies devoid of light chains – VM) they were discovered by studying blood samples and other biomaterials of camels, alpacas, llamas and sharks.

Their discovery prompted Wilson and his colleagues to the idea that such nanoteles can be used as a "constructor" to create a kind of composite antibodies that recognize all three varieties of the influenza virus – A, B and C. 

As a rule, most of the most serious and severe influenza epidemics are caused by viruses from category A, however, two other types of virus are dangerous to human life. The structure of their shell is noticeably different, which is why scientists could not create antibodies that suppress all three subspecies of the virus at the same time, and create a universal cure for this disease.

Wilson and his team took a big step towards realizing this dream of therapists by injecting into the body of several llamas a large number of "fragments" of the shells of two types of influenza – H7 and H2. When the animals' immunity began to react to these fragments, the scientists took samples of their blood and fished out antibodies from them.

Antivirus "lego"

In total, they managed to find four types of nanoteles that respond to influenza – SD36, SD38, SD83 and SD84. Each of them interacted only with some types of virus. For example, SD36 suppressed type A2 influenza, but did not react to class A1 viruses, and SD38 acted in the opposite way.

After analyzing their structure, the scientists identified those areas in the structure of viruses with which they connect, and used this information to "glue" all four antibodies into a single structure, called MD3606. 

Such "multibody", as Wilson and colleagues called them, successfully protected mice from death when infected with three types of avian and swine flu, H1N1, H3N2 and H7N9, as well as from various types of viruses from group B.

This protection, as further experiments have shown, has one drawback. Antibodies are quickly washed out of the body, which is why a person will either have to undergo injections very often, or take very large doses of MD3606 for protection for the whole season. Both will be very expensive and potentially dangerous pleasure. 

Scientists circumvented this problem by inserting a gene containing instructions for the production of this "multibody" inside the AAV retrovirus, from which all potentially dangerous genes were removed. If you inject a spray of such viral particles into the nose of a rodent or a human, they will penetrate into their epithelial cells and cause them to produce MD3606 for several months until they die.

As further experiments on mice showed, such a vaccination protected rodents from influenza for at least two months, which will be enough for "full protection" of a person throughout the season.

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