The first genetic engineering vaccine, the Chinese rabbit industry no longer “talk about plague color change”

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Science and Technology Daily reporter Zhang Ye

“For the rabbit industry, ‘rabbit plague’ is the number one killer.”

In April 2020, the Veterinary Institute of Jiangsu Academy of Agricultural Sciences first discovered cross-border and new rabbit hemorrhagic disease virus type 2 (rhdv2) in China. The mortality rate of this type 2 “rabbit plague” is as high as 90%. Once the virus spreads, China’s rabbit industry will be wiped out.

“In May, we applied to the Ministry of agriculture and rural areas for emergency evaluation vaccine, which is expected to block the spread of type 2 ‘rabbit plague’ in China as soon as possible.” Researcher Wang Fang of the innovation team for prevention and control of major rabbit epidemics of Jiangsu Academy of Agricultural Sciences told reporters.

Since the 1960s, the team has isolated and found a number of bacterial and viral species, and took the lead in developing rabbit plague genetic engineering vaccine in the world, realizing the full coverage of diagnosis, immunization and monitoring technologies of major rabbit diseases, making a significant contribution to China’s rabbit industry ranking first in the world.

Rabbit hemorrhagic disease causing rabbit farmers to “talk about disease discoloration”

Rabbit breeding is a traditional characteristic industry in China. At the same time, China is also a big country for rabbit breeding, with an annual slaughter volume of about 600700 million, accounting for more than 60% of the world.

In recent years, rabbit breeding has become an important industry for poverty alleviation. Especially in western regions such as Xinjiang, Gansu and Sichuan, many large rabbit farms have been built, which plays an important role in local Lbx Pharmacy Chain Joint Stock Company(603883) poverty alleviation and prosperity.

“If you raise three rabbits at home, you don’t worry about oil, salt and vinegar; if you raise ten rabbits at home, you don’t worry about cotton and cloth; if you raise a hundred rabbits at home, you can get rich.” This “getting rich Sutra” has been widely circulated among rabbit farmers.

However, there is a kind of rabbit hemorrhagic disease that makes rabbit farmers “talk about disease and turn pale”, which has swept the world since it appeared in 1984. It is highly infectious and has a high mortality rate. Once infected, rabbits will die within a few days. Therefore, people call it “rabbit plague”.

In order to inhibit the spread of the virus in a short time, people use the most traditional inactivation technology to produce vaccines. Veterinary drug manufacturers inject the virus into healthy rabbits. After rabbits die of disease, take out their liver, kidney and other tissues, grind and inactivate them to make vaccines.

There are defects in this technology: first, the production of inactivated vaccine requires a large number of live rabbits, and China alone needs Shanghai Pudong Development Bank Co.Ltd(600000) rabbits every year; Second, the biosafety is poor, because in the process of grinding and crushing, the aerosol with virus will spread in the air without any leakage; Third, this method can not be large-scale production.

The world’s first genetically engineered subunit vaccine against rabbit plague was approved

Both rabbits and humans belong to mammals and have the same immune response function. The immune system will produce immune response and immune memory to antigen substances in vivo or in vitro, so that each pathogen can be “remembered” by the immune system through characteristic antigen epitopes.

In order to solve the problem of inactivated vaccine, Wang Fang’s team designed and constructed a recombinant virus, in which the protective antigen of rabbit plague virus can be expressed.

“This virus is called recombinant baculovirus. One of its characteristics is that it does not infect vertebrates such as mammals. Therefore, it is very safe for humans.” Wang Fang said.

The survival of the virus must depend on the living body. To make a vaccine with the virus, we must first make it replicate in the cell. The reporter saw that the researchers filled the fermentation tank with a yellow liquid as the culture medium, cultured a large number of cells, and then injected the recombinant baculovirus into the tank to allow the virus cells to replicate on a large scale. Finally, these cultures were inactivated and made into vaccines.

In 2017, the world’s first genetic engineering subunit vaccine of rabbit plague developed by Jiangsu Academy of Agricultural Sciences won the national class I new veterinary drug registration certificate, ending the embarrassing history of manufacturing vaccines with rabbit infected tissues.

Race between new vaccine and type 2 rabbit plague virus

One wave will flatten and another wave will rise. In 2010, rabbit hemorrhagic disease type 2 (rhd2) first broke out in France, soon spread throughout Europe, and then became popular all over the world. Different from covid-19 virus infected by human beings, the virulence of rhdv2 has increased with time, and the mortality has reached 90%.

In April 2020, a large number of rabbits died suddenly in a Chinese farm. After receiving the samples submitted for inspection, Wang Fang’s team confirmed that this was the first discovery of a new rabbit plague virus – rabbit hemorrhagic disease virus type 2 in China through gene sequencing and comparative analysis.

Type 2 rabbit plague virus is not only highly toxic, but also can infect other rodents across species, which is very harmful to ecological security. At present, there is a lack of effective prevention and control means.

However, long before the emergence of type 2 rabbit plague in China, Wang Fang’s team closely followed the changes of foreign rabbit plague, conducted preliminary technical research, created a specific diagnostic method for type 2 rabbit plague and obtained rhdv2 virus antigen protein. After receiving the infected rabbit samples in China, they quickly started the development of a new type of vaccine and became one of the first units to submit vaccine emergency evaluation to the Ministry of agriculture and rural areas in China.

“In the research of type 1 rabbit plague vaccine, we have improved the technical system of rabbit disease prevention and control and achieved full coverage of diagnosis, immunization and monitoring, so we can detect type 2 rabbit plague at the first time and develop a new vaccine.” Wang Fang said.

At the same time, in order to reduce the cost of rabbit farming, they have also successfully created a series of rabbit vaccines, such as the dual and triple vaccines for the prevention of rabbit plague, Pasteurella multocida and Clostridium perfringens type A, so as to realize the full protection of serious diseases and one shot prevention of multiple diseases.

At present, Jiangsu Academy of Agricultural Sciences is developing a new bivalent rabbit hemorrhagic disease vaccine, a new gastrointestinal disease vaccine and a new respiratory disease vaccine, and plans to establish a national rabbit disease monitoring, diagnosis and control service center to continuously monitor the prevalence of rabbit disease and make rapid and accurate diagnosis.

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