This disease specifically harms children, has a mortality rate of up to 30%, and is spread by mosquitoes...

The most enjoyable thing about summer is eating ice watermelon, and the most annoying thing is mosquitoes.

The reason we hate mosquitoes is not only because they give us "little red envelopes" that make us itchy, but also because they spread diseases, such as epidemic encephalitis Japanese (JE).

Mosquito, image source: pexels

Japanese encephalitis, like the recently reported monkeypox, is a zoonosis that primarily affects children under 10 years of age.

There is still no specific and effective medicine for this disease. Fortunately, thanks to the efforts of Chinese scientists, the harm of this disease has been greatly reduced because of the development of vaccines.

Today we will talk about the birth process of the Japanese encephalitis vaccine.

0 1

A great mission from heaven

In the early 1950s, an epidemic of Japanese encephalitis broke out in North China, with an incidence rate of 20/100,000, and even 41.3/100,000 in some areas. For a time, hospitals were overcrowded, and even the corridors were filled with encephalitis patients.

To deal with zoonoses, reducing the source of infection is one idea, and developing targeted drugs is another idea. The Patriotic Health Campaign has greatly reduced the number of mosquitoes, but it cannot be completely eliminated for the time being; and as mentioned earlier, effective drugs have not been found to this day. Therefore, there is only one way left: to develop a vaccine as soon as possible.

In order to let the scientists understand the urgency of the task, Beijing organized them to visit the Children's Hospital. There, children who should have been jumping around could only lie in bed; some parents, hearing that treatment would cost a lot of money and might leave sequelae, simply abandoned their children in the hospital.

One of the visitors was Yu Yongxin. He was born in a poor family and originally wanted to study medicine, but because he was seriously ill during college, he had to change his major to study biology. After graduation, he was assigned to the Ministry of Health's Biological Products Inspection Institute, responsible for the inspection and research of viral vaccines. Unexpectedly, he once again got the opportunity to face the disease.

Yu Yongxin

So the question is, how to make a vaccine? Speaking of this, we cannot fail to mention poxvirus infection.

Poxviruses are viruses that can cause acne (papules, herpes) on humans and vertebrates, including orthopoxvirus, avipoxvirus, etc. The recent monkeypox, caused by monkeypox virus, belongs to the orthopoxvirus genus; and the most famous of them is smallpox.

To put it bluntly, vaccines are mock exams. Cowpox and smallpox have the same test type (antigenicity), but the difficulty (pathogenicity) is much lower. With cowpox practice, our immune system can deal with smallpox. In fact, the smallpox vaccine is also effective against monkeypox.

In the 1930s, American scientist Ernest William Goodpasture became interested in poxviruses; and to study viruses, one must first culture them. As the name suggests, avipoxviruses mainly infect poultry, so can they infect eggs?

Chicken embryo under light

It was this unintentional act that opened the door to virus research: the results showed that fowlpox virus could be cultured in chicken embryos; later, Australian scientist Sir Frank Macfarlane Burnet discovered that many viruses could grow in chicken embryos, and in this process the virulence of the virus would decrease.

The reason is not complicated. As the saying goes, survival of the fittest. When a virus enters an unfamiliar environment, it will be forced to constantly change; after the change, the harm of the virus to humans may be reduced.

At this point, the idea was clear: to develop a Japanese encephalitis vaccine, it was necessary to reduce the pathogenicity of the virus while retaining its antigenicity; and using chicken embryos for continuous passage might reduce the virulence of the virus. Yu Yongxin quickly mastered the relevant technology through hard self-study and the guidance of his predecessors, and plunged into the laboratory.

02

Twists and turns

However, things are always easier said than done.

The laboratories at that time were far from as spacious as they are now, and air conditioning was out of the question. In the cramped and hot environment, researchers had to be careful to avoid bacterial contamination and damage to the experiments. The most frustrating thing was the result - Yu Yongxin spent three years and conducted nearly a thousand subculture experiments, but still failed to reduce the virulence of the virus to an appropriate level.

Could it be because of the chicken embryo? What about changing the culture environment?

Scientific exploration requires solid knowledge and skilled skills, but it also requires the courage to break new ground. For example, when people first started studying polio virus, they took it for granted that it could only grow in the nervous system of higher animals. Therefore, 17,000 monkeys were sacrificed just to classify the virus. The money spent on this is a small matter. The key is that the number of monkeys is small, it is difficult to raise them, and a round of experiments takes a long time. Can those who are sick afford to wait?

Later, American scientist John Franklin Enders discovered that polio virus can grow in other tissues. The sugar pills developed by Gu Fangzuo were produced using monkey kidney cells in the early years.

Sugar pills, once produced using monkey kidney cells

Yu Yongxin is also a courageous person. After failing to attenuate the virus in chicken embryos, he began to try to culture the virus using mouse kidney cells, spleen cells, and subcutaneous tissue, and finally obtained a strain with significantly reduced virulence, SA14-5-3.

Vaccines are a matter of life and death. Theoretically feasible is not enough. They must also be tested by facts. The results of clinical trials were nothing short of a cold shower: the virus did not cause adverse reactions, but its antigenicity was not very strong. The antibody levels of some vaccine recipients dropped rapidly, and some vaccine recipients did not produce any Japanese encephalitis antibodies at all.

03

You're done!

It has been more than 20 years since Yu Yongxin received the scientific research task. It took a generation of people to do one thing, but got such a result. If it were someone else, they would probably be depressed, collapsed, or even give up on themselves. But Yu Yongxin did not give up, but got busy again for the patients in the children's hospital.

After a calm analysis, he believed that there were two ways to increase antigenicity: one is to increase the virus's reproductive capacity. With more viruses, the stimulation to the immune system is greater, and the antibodies produced will also increase accordingly; the other is to use plaque purification to screen out the most antigenic viruses from all safe viruses.

At this point, someone will definitely ask, what is plaque purification?

Plaque purification involves another zoonosis, Western equine encephalitis. Western equine encephalitis is caused by Western equine encephalitis virus. In the 1950s, Italian virologist Renato Dulbecco came into contact with this virus while studying in the United States. He found that the virus formed plaques of varying sizes in a culture dish.

Plaques formed by Western equine encephalitis

In the past two years, people have often discussed "new crown variants". What exactly is a "variant"? In fact, it is a virus that contains specific gene mutations. A virus invades a cell and can produce thousands of offspring; because of gene mutations, the genetic material between each offspring is not the same. After multiple mutations, some offspring may change in antigenicity and pathogenicity, and they are called a new strain. Different strains have different destructive abilities to cells, so plaques of different sizes will form on the culture dish. Conversely, this effect can be used to purify and separate viruses.

Relying on these two methods, Yu Yongxin discovered a new strain, SA14-14-2. Studies have shown that it is not only safe but also highly antigenic.

After that, there was a series of victories: in 1989, the live attenuated Japanese encephalitis vaccine prepared with the SA14-14-2 strain obtained a production license; in 1990, this research won the first prize of the National Science and Technology Progress Award; in 2002, the vaccine was exported to South Korea, which was the first time that a human biological product developed by my country was transferred abroad; in the same year, the vaccine was recommended by the World Health Organization...

04

end

Today, Yu Yongxin's vaccines have been used to vaccinate more than 600 million children, and tens of millions of doses are exported to South Korea, India, Thailand, and Nepal every year. Generations of children have grown up healthily under the protection of vaccines, and Japanese encephalitis has become a disease that is not well understood.

When looking back on the past, Yu Yongxin said that he could not have achieved such results without the support of his leaders and the help of other colleagues.

In my opinion, two more points should be added: one is the mastery of professional skills and standing on the shoulders of senior scholars; the other is the indomitable spirit and the courage to explore unfamiliar paths.

It is with this spirit that mankind can continue to defeat diseases, the incidence of various infectious diseases including zoonoses can become lower and lower, and we can have peace in the era of epidemics.

References

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