From fry to large: the first DNA vaccines in Russia will increase fish production

Russian scientists are creating DNA vaccines for fish, which will allow a record increase in survival in aquatic farms and increase their productivity. The specialists conducted the first pilot experiment, investigating a prototype of such a drug on walleye, in the conditions of industrial aquaculture in the Leningrad region. According to experts, aquaculture suffers most from bacterial and viral diseases, so the development of domestic drugs is extremely relevant. For more information, see the Izvestia article.

Vaccination of fish

Scientists of the branch of the Institute of High-Molecular Compounds of the St. Petersburg Institute of Nuclear Physics named after B. P. Konstantinov (PIAF-IFS), which is part of the Kurchatov Institute, together with colleagues from the St. Petersburg branch of the All-Russian Scientific Research Institute of Fisheries and Oceanography and the State Scientific Center of the Institute of Bioorganic Chemistry named after Academicians M.M.Shemyakin and Yu.A.Ovchinnikova RAS (Moscow) is developing a prototype DNA vaccine for fish. This summer, researchers conducted the first pilot experiment on walleye in industrial aquaculture in the Leningrad region. His goal was to compare the effectiveness of the prototype vaccine with different methods of administration: oral, injectable, immersion (immersion method).

However, as scientists told Izvestia, they are not currently faced with the task of creating a vaccine against any particular pathogen affecting aquatic life.

— The methods of genetic engineering in the modern world are quite well developed and it is not difficult to first insert the "necessary gene" (for example, the X virus envelope gene) into the DNA vaccine being developed, and then scale production. It is much more difficult to understand how a particular type of vaccine works, and how to increase its effectiveness when administered in the most "friendly" way for fish. It is these questions that we are looking for answers to as part of our research," Anastasia Zubareva, a researcher at the Laboratory of Natural Polymers of the Kurchatov Institute branch of the Scientific Research Center, PIAF—IVS, Candidate of Chemical Sciences, told Izvestia.

Scientific interest: the status of the clownfish and the mystery of the origin of lightning

Izvestia collected the top 5 research news for the week

According to her, now one of the tasks of scientists is to study the biodistribution of the prototype vaccine in various organs of fish, which will help track the path of formation of the immune response. A circular DNA molecule (plasmid) helps in this, into which the green fluorescent protein (GFP) gene is inserted, one of the most famous fluorescent labels for cellular and molecular biologists. With the help of such luminous molecules, scientists can visualize and study various biological processes.

The second task is to increase the effectiveness of non-injectable forms of DNA vaccines.

— Currently, the main method of administering vaccines to fish is injections. But imagine that there are tons of slippery patients waiting in line. Norway, one of the world's leading producers of aquaculture products, solved the problem by creating a special installation. It is controlled by a single operator, while it is capable of inoculating up to 40 thousand salmon fry and simultaneously administering up to four vaccines. But there is an alternative — oral and immersion routes of administration of the drug," she said.

The developers believe that immersion vaccination of fry should be the preferred method. To do this, the fish is briefly deposited in tanks containing the drug, and then returns to its habitual habitat. This method will allow you to process a large number of fish at the same time without severe stress for them.

How DNA vaccines work

The research team will have to carry out a whole range of research: they are still at the beginning of their journey. In order for the DNA vaccine to reach its target and enter the cell nucleus, it needs to overcome many biological barriers: the epithelium of the skin, gills, and intestines.

— To increase the bioavailability of the prototype vaccine, we propose to package the plasmid in a shell made of polymers of natural origin — alginate and chitosan. It will protect DNA from premature destruction in the harsh conditions of the gastrointestinal tract and, possibly, will increase the effectiveness of oral vaccination. As for the second route of administration, "vaccine baths," in this case, positively charged chitosan can be added to the vaccine. It has the ability to adhere to the gill epithelium and temporarily open the tight contacts connecting the cells, increasing the effectiveness of vaccination," noted Anastasia Zubareva.

At the same time, according to scientists, the introduction of DNA vaccines in Russia may face a number of difficulties related to regulatory restrictions on the use of GMOs.

— But the world is changing. Not so long ago, we witnessed the rapid introduction of vaccines containing nucleic acids into practice when humanity was in dire need of effective immunopreparations during the COVID-19 pandemic. Such rapid promotion of drugs to the market became possible only because scientists had a lot of knowledge about how such vaccines work, and ready-made developments were waiting in the wings. Therefore, our task today is to understand the mechanisms of action of such drugs, evaluate their effectiveness and, if necessary, adjust to the needs of specific aquatic farms," said the researcher.

Waiting for a paw: veterinarians complain about the lack of vaccines for cats and dogs

This can lead to infection with dangerous diseases not only of animals, but also of humans, doctors warn.

Global experience of DNA vaccination and statistics

Such vaccines are not new to global aquaculture, scientists told Izvestia. For example, in 2005, this type of drug had already saved Canadian salmon from infectious necrosis of hematopoietic tissue, and many aquatic farms from bankruptcy. According to scientific sources, in some cases it was possible to achieve 80-100% survival after vaccination compared to 0-20% without it.

According to statistics, the volume of aquaculture production in Russia is growing from year to year, however, an important factor in preserving products is the reduction in the percentage of fish deaths in Russian fish farms. Currently, up to 5% of products die from virological, bacteriological and parasitological diseases, the head of the Smart Supply Chain segment of the FoodNet working group told Izvestia NTI Sergey Kosogor.

"The development of DNA vaccines by the Russian Federation will have a positive impact on increasing fish production and will increase the survival rate of aquatic organisms, including juveniles, which are most vulnerable to diseases," said the specialist.

Aquaculture suffers the most from bacterial and viral diseases, Andrey Martsinkevich, head of the Moscow Testing Reference Laboratory at the Rosselkhoznadzor's National Center for the Safety of Fish and Agricultural Products, told Izvestia. The list of such diseases in the territory of the Russian Federation is not unique.

— Fish diseases in aquaculture conditions spread extremely quickly due to the density of planting, which often allows direct contact of fish with each other. At the same time, making an accurate diagnosis takes a considerable amount of time, and significant losses may already occur before the start of targeted treatment. Therefore, prevention is the most effective means of protecting against diseases," the specialist said.

Vaccination is especially effective in the early stages of the body's development. For example, specialists from the All-Russian Scientific Research Institute for Animal Welfare have now developed a multivalent vaccine for salmonids, which is expected to be effective against both viral and bacterial infections, said Andrey Martsinkevich.

However, it is wrong to write off all waste as pathogens, Anton Alekseev, the head of the Aquaferm farm, noted in a conversation with Izvestia. According to him, the root cause of fish deaths in farms is most often the temperature, water quality, planting material and feed.

— Different aquaculture facilities have different causes of death: waste on sea salmon can reach 70% of sea lice, and rainbow trout similar to it for consumers can reach such cull figures due to heat rather than pathogens. I assess the prospects for the development of domestic vaccines as high, although it may take time before stable results in this direction," the expert said.

According to him, research needs to continue, and the importance of moving towards import substitution of these vaccines cannot be overestimated.