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Coronavirus

Japanese scientists turn to silkworms for COVID-19 vaccine

Oral form using ground-up pupae may prove effective against deadly disease

Kyushu University professor Takahiro Kusakabe and his team are working to develop a unique vaccine using silkworms. (Photo by Akihiko Nishiyama)

TOKYO -- As scientists the world over scramble to develop a vaccine for the coronavirus, Kyushu University professor Takahiro Kusakabe and his team are working to develop a unique vaccine using silkworms.

In his project, each of the worms is a factory that manufactures a type of protein to serve as the key material for vaccine production. Kusakabe said it is possible to create an oral vaccine and aims to start clinical tests on humans in 2021.

In a building on the Kyushu University campus in Fukuoka, in western Japan, "we have about 250,000 silkworms in about 500 different phylogenies (family lines)," Kusakabe said.

In his lab a short distance away from the building, student volunteers with special permission from the university are hard at work on vaccine development. Nikkei spoke to Kusakabe in May, when Japan was under a state of emergency.

The team has mapped out a research plan to develop an effective vaccine.

Genes of the protein that forms the outer "spikes" of the new coronavirus are incorporated into the virus and injected into a silkworm. The virus is then taken into silkworm cells, and after about four days, spike proteins that can serve as vaccine material start to be produced in large quantities. These spike proteins are removed, refined and made into a vaccine that is administered via injection.

From the thousands of insects in the lab, "we have found a type of silkworm that can efficiently manufacture the proteins," Kusakabe said.

In Japan, Anges, a biotechnology company established by Osaka University researchers, leads the way in coronavirus vaccine development. A DNA vaccine being developed by the company is aimed at sending genes of the spike protein into the human body, inducing the body to create the proteins and induce immunity to the virus.

By contrast, Kusakabe's team aims to produce spike proteins using silkworms, rather than the human body. This is believed to be safer than attenuated vaccines, in which a weakend form of the virus is introduced into the body.

Kusakabe plans to work with the university's School of Pharmaceutical Sciences to test the vaccine on animals. First, he plans to inject spike proteins taken from silkworms into mice to see if this creates antibodies to block coronavirus infection. He will then check if the antibodies can actually block the virus's intrusion into cells.

He aims to complete animal testing by early 2021 and then start clinical testing on humans.

"Using silkworms, you can shorten the time it takes to produce candidate substances for the vaccine to as little as about 40 days," Kusakabe said, adding that costs for producing vaccines will also be reduced as the silkworm method does not require large equipment.

Two years ago, Kusakabe launched Kaico, a startup that commercializes research findings at the university. So far, the company has introduced laboratory chemicals, such as an enzyme made using silkworms. It was developing vaccines for coronaviruses that infect chickens and pigs, which cause serious problems in animal husbandry.

It was at that point that the novel coronavirus surfaced in the Chinese city of Wuhan, which prompted the team "to move up the development schedule," Kusakabe said.

His team has come close to completing a coronavirus diagnostic drug using spike proteins, while simultaneously working on a project to develop an oral vaccine using silkworms. The latter is a vaccine made by injecting a virus incorporated with genes of spike proteins into silkworm pupae.

Many people in China, Southeast Asia, Latin America and Japan, representing half the world's population, eat insects as a key source of protein.

People might cringe at the thought of eating bugs, so pupae could be ground into powder and formed into tablets or capsules.

"Pupae do not have intestines, and so their proteins are not destroyed by digestive enzymes when they are ground into a powder," Kusakabe said. "You can take in a far larger amount of proteins [by eating pupae] than you can by getting them in an injection, so I think that could allow it to have a great result as a vaccine."

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