Flu vaccine: antiviral virus
Virus against influenza
Scientists have set another virus on the flu virus,
by equipping him accordinglyNadezhda Markina, Newspaper.
To cope with any flu virus and protect humanity from future pandemics, researchers suggest using gene therapy. Moreover, there is nothing terrible in the gene therapy itself: the antibody gene in the viral vector can be delivered to the destination simply by dropping it into the nose.
By this method, it was possible to deliver broad-spectrum antibodies to the body that neutralize the influenza A virus of various subtypes. The results of testing the new approach on mice and ferrets were published by an international group of scientists led by James Wislon (University of Pennsylvania, Philadelphia) in the journal Science Translational Medicine (Limberis et al., Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza).
The researchers emphasize the imperfection of the current means of combating the flu virus. The immune response to a natural virus or to a vaccine is limited to a single subtype of the virus. Therefore, vaccination against seasonal influenza will not protect against a new subtype, which usually arises from a virus circulating in animal populations after it acquires the ability to infect humans.
Recently, scientists have high hopes for broad-spectrum monoclonal antibodies (mAbs). This term refers to molecules that are produced in one (mono) type of B-lymphocytes. It has been shown that human mAbs can neutralize different subtypes of the influenza A virus, including all known pathogens of seasonal influenza and pathogens of pandemics that occurred in the XX century. This is due to the fact that they react to a very conservative site of the viral protein-antigen – hemagglutinin, which practically does not change. But their use as vaccines is impractical: these proteins circulate in the blood for a limited amount of time, and they would have to be injected too often.
An alternative way is to make proteins synthesize in the right place, for which it is necessary to deliver their genes there. This is what gene therapy is used for. Maria Limberis, the first author of the work, and her colleagues used an adeno-associated virus (AAV) for delivery, which has already served as a vector in gene therapy. This was convenient because AAV uses the same "gate" as the influenza virus to enter the body: it is introduced into the cells of the respiratory tract.
The therapeutic AAV virus had to be loaded with useful baggage. Scientists have cloned a gene for a broad-spectrum human antibody called Fl6. They added all the necessary additives to this gene and inserted a genetic construct into the genome of the AAV virus. A suspension of the genetically modified virus was instilled into the nose of mice that had previously been infected with lethal doses of H1N1 and H5N1 viruses. Moreover, different isolates of these subtypes of viruses were used in different groups of mice, including the pathogens of the 1918 and 2009 influenza pandemics.
The complexity of the approach was to force cells that usually do not do this to produce antibodies, that is, not lymphoid cells, but epithelial cells of the respiratory tract and lungs, the researchers explain.
The treatment was successful: the experimental mice survived, unlike the control animals, which had to be euthanized due to their serious condition.
The analysis showed that in the cells that received a dose of the gene therapy virus, the influenza virus sharply decreased its number. At the next stage, the new method was tested on ferrets (which are considered a more adequate model of human flu) – and also with good results.
"We have experimentally tested a concept that is designed to protect humans from the flu pandemic with broad–spectrum antibodies," Wilson said. "In the future, we are going to test our approach on a subtype of the Chinese H7N9 avian influenza virus."
Although encouraging results have been obtained on animals, it is necessary to carefully assess the safety of this approach for humans, as well as to check for how long it provides protection against the influenza virus, scientists emphasize. Now they are working with several companies to accelerate the development of a product – a preventive gene therapy vaccine.
Portal "Eternal youth" http://vechnayamolodost.ru31.05.2013