Antiviral viruses
Leningrad flu viruses turned into "zombie kamikaze" to protect children
The staff of the Institute of Experimental Medicine proposed a variant of a vaccine against respiratory syncytial virus (RSV), which is based on a live weakened influenza virus. At the same time, information is added under the shell of the influenza virus, which allows the recipient body to quickly recognize RSV and effectively fight it. The scientific article was published in the journal Human Vaccines & Immunotherapeutics. The work is supported by an RNF grant.
The human respiratory syncytial virus affects the lower respiratory tract - the bronchi and their smaller branches, the bronchioles. The immunity of adults, as a rule, copes with it quite easily, but children, especially in the first year of life, often develop bronchiolitis or even pneumonia due to RSV. Therefore, it makes sense to vaccinate children against respiratory syncytial virus.
One of the promising areas of vaccine development is the creation of drugs that can be delivered to the right cells by so–called viral vectors. In fact, such vectors are viruses that normally attack a person (or another recipient of the vaccine), but modified in such a way that they cannot cause the disease. Since a number of viruses are able to embed their genetic material into the DNA of the host, the vector genes can be changed in such a way that they contribute something necessary and useful to researchers. This is exactly what they do when creating transgenic animals. At the same time, the rabies virus or even HIV-like retroviruses are used. However, it can be dangerous to use them in medicine, since it is not entirely clear how the human body, especially a very small one, will react to them.
Therefore, experts from the Institute of Experimental Medicine in St. Petersburg suggested using as a carrier a virus whose effects on the human body have been well studied - the influenza virus. It is already used as part of vaccines: a live, but weakened form of the influenza virus is administered to those who want to protect themselves from the corresponding disease. It was she who formed the basis of the experimental RSV vaccine.
The main "fighters" of human immunity are T-killers – cells that destroy foreign objects, previously recognizing them by fragments of certain molecules on their surface. Such fragments are called epitopes. It was they who became the main "stuffing" of the new vaccine. However, inside weakened influenza viruses, epitopes were present not in the form of "pieces" of RSV proteins, but in the form of sequences of RNA nucleotides encoding these "pieces". Scientists have embedded these sequences into genes encoding proteins of the influenza virus (its genome is represented by RNA, not DNA). In other words, the new respiratory syncytial virus vaccine consisted of influenza viruses (H7N9 or A/Leningrad/134/17/57 ), in which, between their own genes, there were sites encoding fragments of human RSV envelope proteins. After the weakened influenza viruses multiplied, the number of epitopes available for recognition by T-killers increased, and the overall immune response increased.
The vaccine was tested for cytotoxicity – the ability to kill cells of the body into which it was injected. The test was performed on mouse spleen cells. The ability of the drug to achieve the goal and activate immunity was determined by the concentration of gamma interferon, the number of active T-killers that recognize RSV, and the percentage of mice that became ill after vaccination. These experiments revealed that the experimental influenza vaccine does not have cytotoxicity and effectively distributes information about how the human respiratory syncytial virus "looks".
An experimental vaccine based on live attenuated influenza viruses has at least two advantages. Firstly, it can be injected intranasally, that is, in the form of a spray into the nostrils (after all, it is mainly by airborne droplets that influenza viruses spread). Secondly, both H7N9 and the St. Petersburg, cold-resistant strain A/Leningrad/134/17/57 , and their closest relatives activate many processes and cell types in the immune system at once when they enter the body. This ensures that the vaccination will not go to waste.
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