24 May 2013

Universal nanovaccine against influenza

A new universal flu vaccine was created from nanoparticles

Copper news based on Nature materials: 'Universal' flu vaccine effective in animalsA group of specialists from the National Institute for the Study of Allergic and Infectious Diseases of the USA has developed and successfully tested on an animal model a universal flu vaccine based on the use of self-ordering protein nanoparticles synthesized in the laboratory.

The work was published on May 22 in the online version of the journal Nature (Kanekiyo et al., Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies).

The team led by Gary Nabel used molecules of hemagglutinin, the surface protein of the influenza virus, which ensures its ability to attach to the host cell (the production of antibodies to hemagglutinins causes the main immunity to the influenza virus), and ferritin, a protein that acts as the main intracellular iron depot and naturally forms spherical clusters, when creating nanoparticles of 24 identical polypeptides.

In each nanoparticle, hemagglutinin molecules are genetically "fused" into a ferritin molecule in such a way that the resulting complex spontaneously self-organizes into a structure with a ferritin core through which eight trimeric hemagglutinin spikes "germinate", similar to how these protein spikes cover the surface of the influenza virus.

"We have synthesized a completely new molecule that has never existed before and, what is especially cool, it orders itself," said Nabel in this regard.

According to the authors, after immunization with such nanoparticles of mice and ferrets, the levels of production of antibodies to the virus in the first of them were 34 times, and the second – 10 times higher than when using conventional vaccines (the level of antibody production directly correlates with the level of protection from the virus).

According to Nabel, such a strong response is due to the fact that hemagglutinin spikes located on the surface of nanoparticles, unlike a virus, do not hide among other surface proteins and therefore are better represented by the immune system.

The universality of the new vaccine is ensured by the fact that the neutralizing antibodies produced bind to those parts of the hemagglutinin molecule that are unchanged in different strains of the influenza virus. One of these sites – the site of binding to the receptor – is located in the head of the molecule and is responsible for the recognition of the host cell, and the second is responsible for the penetration of the virus through its membrane.

As the authors point out, nanoparticles involving hemagglutin of the H1N1 influenza virus strain that circulated in 1999 were able to protect ferrets from many other strains as well, including one of the 2007 strains that did not exist in 1999.

The authors of the vaccine plan to begin its human trials, as well as to develop cost-effective methods of its production. In addition, the Nabel group plans to develop vaccines against HIV and herpes virus based on the same technology of "melting" proteins into a ferritin base.

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