13 August 2012

Against everyone!

The flu broke the trunk

Sofia Neskuchnaya, "Newspaper.Ru»An antibody active against all types of influenza virus has been found.

It attacks an element common to all strains, forbidding the key protein of the virus to change shape and thus blocking the penetration of infection into cells. To create a universal vaccine, scientists can only completely copy the action of this antibody.

All influenza viruses dangerous to humans belong to two large groups of strains – A and B. Influenza virus strains B are considered less dangerous than strains A. They have been studied less because it is almost impossible for them to mutate into a deadly strain that will provoke a pandemic. Despite this, type B strains are responsible for a large number of cases of the common flu every year. Both types (unlike type C strains) are dangerous due to their extremely variability: every year they adjust to the environment, vaccines and a lot of other external factors, making it very difficult to create a truly universal remedy for this ailment.

And in order to find it, you need to identify a conservative, unchanging site for all strains, important enough for the virus, so that its blocking makes the particle harmless.

A group of scientists from the Scripps Research Institute (California), in collaboration with the Vaccine Institute in the Netherlands, described in detail three human antibodies that provide reliable protection against the B strain of the influenza virus. Earlier, the same group of scientists had already "dealt" with antibodies to the A strain.

The results of the work are described in a publication in the journal Science (Dreyfus et al., Highly Conserved Protective Epitopes on Influenza B Viruses).

The isolation and detailed characterization of broad-spectrum antibodies opens the way to the development of a universal influenza treatment technique based on the work of these antibodies. It will have to provide really long-term protection against the virus, unlike modern vaccines that work only against a narrow group of seasonal strains.

"In order to develop a truly universal flu vaccine, it is necessary to provide protection against both type A and type B strains, and today we are stating a detailed characterization of antibodies to both of these types," said Ian Wilson, professor of structural biology at the Scripps Institution, who led the work.

One of the antibodies turned out to be particularly interesting: it is able to resist both A- and B-type influenza viruses. "This is the only known antibody in the world that can fight both types," Wilson stressed.

To find antibodies that provide comprehensive protection against A- and B-type strains, scientists have collected a large "collection" of antibodies to influenza viruses from the immune cells of volunteers who were vaccinated against seasonal influenza. Then, from the found antibodies, those that most successfully cope with B viruses were selected. Three antibodies – CR8033, CR8071 and CR9114 – successfully protected mice from the usually lethal doses of the two most common strains of virus B. CR9114 also had activity against A-viruses, including H1N1 swine flu, which killed about 17 thousand people in 2009.

The fact that one of the antibodies turned out to be active for very different types of virus suggests that it binds to a fundamentally important and universal site of the virus common to different strains. Binding sites are called epitopes or antigenic determinants – this is a group of amino acid residues of a protein antigen (or a section of a polysaccharide chain – for example, as part of a glycoprotein) forming a site on its surface that can interact with a complementary site (active center) of the corresponding antibody.

In order to establish the mechanism of action of the universal antibody, it was studied in detail and characterized using electron microscopy and X-ray diffraction analysis. It turned out that CR8033 binds to a highly conservative epitope, sites on the "head" of the key protein of the virus – hemagglutinin. It is he who, being on the outer shell, identifies weak cells and attacks them. CR8071 binds to the base of the "head" of the protein.

The antibody CR9114 binds to the real Achilles heel of the virus – the hemagglutinin stem. "This antibody spatially blocks the protein, preventing it from undergoing the shape change required by the virus to overcome the outer membrane of the host cell. It seems that this is really a weak point of the virus, because this epitope is the same in viruses A and in viruses B," explains Cyril Dreyfus, one of the authors of the work.

Wilson noted that in the work on the study of antibodies to viruses A, made in 2009, a group of antibodies was found that work with the "trunk" of the protein in a similar, but not completely, way. That is why those antibodies were powerless against B-viruses. Now scientists will throw all their efforts into studying the "miracle antibody" - CR9114, in order to learn from it to artificially fight flu of all types.

Portal "Eternal youth" http://vechnayamolodost.ru13.08.2012

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