Scientists at the Perelman School of Medicine at the University of Pennsylvania (USA) have developed a new gene therapy that can protect us from possible epidemics of influenza, according to an Internet publication for girls and women aged 14 to 35. Pannochka. net Dr. James M. Wilson and his colleagues from the Department of Pathology and the Laboratory of Medicine demonstrated how a single dose of adeno-associated virus (AAV) causes the production of antibodies that neutralize the pathogen in the nasal passages in mice and give them complete protection against infection with H5N1 and H1N1 viruses.

These strains were isolated from samples of the historical influenza pandemics of 1918 and 2009.

Dr. Wilson, Dr. Anna Tretyakova and Dr. Maria Limberis, who participate in the Penn Gene Therapy Program, published the results of the research in the online edition of Science Translational Medicine.

In addition to scientists from the University of Pennsylvania, this issue was handled by research teams from Canada and the US: the Canadian Public Health Agency, the University of Manitoba and the University of Pittsburgh. Dr. Tretyakova led the translation studies, and Dr. Limberis was responsible for animal testing.

Dr. Wilson says that their research "has created a technological platform by which to stop virtually any epidemic or biological attack if scientists already have neutralizing antibodies or are readily available". He says that further study of this issue is especially important because of repeated outbreaks of influenza in East Asia, such as the current outbreak of H7N9 in China.

Influenza and its complications are the seventh leading cause of death in the United States, and the world's flu causes 500,000 deaths every year, according to the US CDC. The threat of a new pandemic is constantly hanging over the world, demanding enormous economic costs.

In military circles there is a heightened interest in the development of preventive vaccines for soldiers that would protect themselves from biological weapons.

Antibodies against the virus.

Human antibodies with a wide range of neutralizing effects against viruses exist, but their direct use for the prevention of influenza is very impractical. Today, specific vaccines against seasonal strains that are obtained from chick embryos. This approach strongly depends on the correct prediction of the epidemic of a virus for the coming season.

In this case, strains that from time to time are transferred from domestic animals to humans, do not fit into this scheme, and can lead to unexpected pandemics and human victims. These strains can not be controlled by vaccines developed against other influenza viruses, as it was in 2009. Moreover, the urgent development of vaccines against such sudden epidemics is impractical.

Realizing this, scientists at the University of Pennsylvania proposed a new approach that does not require the initiation of an immune response, the production of antibodies, their purification and the preparation of vaccines. However, the approach is effective against any strain of the influenza virus.

Scientists using the AAV virus introduce a gene that encodes antibodies against many strains of influenza. Genetic engineering allows you to change cells that line the nasal mucosa, and they start producing these antibodies. Simply put, the cells of the mucosa themselves secrete a medicine for influenza.

The most suitable sites for creating modified cells are the mucous membranes of the nasal passages and oral cavity. Normally, antibodies against influenza produce B-lymphocytes, so one of the challenges for scientists was to develop a vector for delivering the desired gene from lymphocytes to completely different, epithelial cells of the respiratory tract. But scientists were able to do this and achieved the production of quite normal protective antibodies.

To this end, the adeno-associated primate AAV9 virus was used, which was discovered in Dr. Wilson's laboratory and was previously studied by Dr. Limberis for the treatment of cystic fibrosis. AAV viruses are known for their ability to transfer and integrate their DNA into the DNA of the host cell. Scientists constructed a genetic "load" for AAV9 and forced it to integrate this gene into the DNA of epithelial cells.

Testing in mice.

The effectiveness of gene therapy was tested in mice exposed to three lethal strains of the H5N1 influenza virus and two strains of H1N1, including the virus of the famous "Spanish".

In mice that had previously been subjected to gene therapy with the AAV9 vector, the virus could not multiply, and the animals did not fall ill. In animals from the control group, the virus developed rapidly, causing a typical picture of the disease. The effectiveness of gene therapy was also confirmed in laboratory fretts.

Dr. Limbers said:

"The novelty of our approach is that we use AAV to deliver a gene that encodes antibodies directly into mucosal cells. This is a non-invasive, painless method compared to vaccination ".

Now scientists are working with commercial intermediaries for the accelerated development of a new product for the prevention of pandemics. Also, scientists hope to create funds for the prevention of dangerous infections in biological attacks for the military and civilians.

medbe. en.

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