Tokyo researchers are working towards ‘dreaming’ COVID-19 vaccine that provides protection for life

Researchers in Tokyo are developing a “dream” COVID-19 vaccine that provides lifetime efficacy in what would be a game-changer when the fight against coronavirus drags on in its third year.

At a time when it appears that most COVID-19 vaccines will require periodic boosters due to a decrease in the recipients’ antibody levels, the creation of a vaccine with longevity efficiency can lead to huge economic savings globally and give the world the upper hand. against coronavirus. , which has infected more than 270 million people and claimed more than 5 million lives around the world.

Shortly after the pandemic began, in early 2020, Michinori Kohara, an emeritus researcher at the Tokyo Metropolitan Institute of Medical Science, wondered if it was possible to develop a vaccine based on the proven smallpox vaccine – which helped the world eradicate it. fatal disease. The vaccinia virus used in the smallpox vaccine is a topic he has been working on for over three decades, and Kohara knows for himself how significant a vaccine that provides strong protection for life can be.

The smallpox vaccine was developed by the British physician Edward Jenner in 1796 to combat the infectious disease, which had an extremely high mortality rate. There have been no patients in Japan since 1956, and the government’s periodic vaccination ended in the late 1970s. The vaccine remains the only shot that has successfully eradicated an infectious disease, the last known case being a patient in Somalia in 1977 following a coordinated global vaccination campaign by the World Health Organization.

So in April 2020, Kohara, in collaboration with the National Institute of Infectious Diseases, began developing a recombinant vaccinia virus containing the tip protein from the SARS-CoV-2 virus, which causes COVID-19. They selected the non-pathogenic strain of the vaccinia virus variant called DIs, which acts as an extremely effective and safe viral vector for the delivery of the SARS-CoV-2 spike gene.

While the messenger RNA COVID-19 vaccines developed by Pfizer Inc.-BioNTech SE and Moderna Inc. has been successful in preventing serious illness and death, neutralizing antibodies drop significantly over six months after vaccination, making boosters necessary – especially against the omicron variant.

In contrast, the vaccine, which Kohara spearheads, can produce potent neutralizing antibodies within a week of inoculation and induce the strongest cellular immunity of any vaccine, he says. This would be significant as none of the currently available COVID-19 vaccines appear to offer long-term protection.

Experiments with mice using the recombinant vaccinia virus encoding the highly pathogenic avian influenza HA gene have shown high antibody levels, which were maintained for more than 20 months, or almost the average lifespan of a mouse, and all vaccinated mice infected with avian influenza 20 months after vaccination survived. In contrast, the unvaccinated mice all died.

Michinori Kohara, Emeritus Researcher at Tokyo Metropolitan Institute of Medical Science |  THE TOKYO METROPOLITAN INSTITUTE OF MEDICIC SCIENCE
Michinori Kohara, Emeritus Researcher at Tokyo Metropolitan Institute of Medical Science | THE TOKYO METROPOLITAN INSTITUTE OF MEDICIC SCIENCE

The project, in which Tokyo Governor Yuriko Koike has expressed his enthusiasm, has been carried out as part of special research sponsored by the Tokyo Metropolitan Government.

“I have worked on various vaccine technologies such as adenovirus and messenger RNA, but the vaccine that uses the vaccinia virus vector is the most powerful of all with few side effects,” Kohara told The Japan Times in an interview. “The hallmark of this vaccine is that it can induce antibodies and lifelong immunity. A shot of the vaccine retains its effect for more than 20 months and there is no other vaccine that can achieve these effects.”

Tests on crab-eating macaques also showed that the vaccine protected primates from developing pneumonia and that the amount of virus detected in their lungs was below the detection limit seven days after coronavirus infection.

The domestic pharmaceutical manufacturer Nobelpharma Co. is set to conduct the first and second phases of clinical trials with Kohara’s vaccine in Japan by the first half of 2023 on 150 to 200 volunteers, including those who have experienced infections and fully vaccinated individuals. If efficacy and safety are confirmed, the final clinical trial is set to start immediately thereafter, with commercialization targeted by 2024 at the earliest, he says.

One of the biggest obstacles to the vaccine is securing the tens of billions of yen needed to complete the latest clinical trial, as Kohara says Nobelpharma cannot finance it alone. Although the government has allocated more than 100 billion yen to subsidize large clinical trials conducted by domestic drug manufacturers, there has been no plan to subsidize the project’s clinical trials, as Nobelpharma and the Tokyo Metropolitan Institute of Medical Science have no previous experience in commercializing a vaccine, Kohara said.

“I hope the government will change its mind when the first two phases of clinical trials show efficacy in humans,” he said. “Or we would look at conducting the trial in collaboration with a major drug manufacturer as a more promising choice,” he said.

While testing on mice has shown that one shot would induce enough neutralizing antibodies for lifelong protection within a week of vaccination, Kohara said two shots taken at three-week intervals have increased the neutralizing antibodies tenfold.

Kohara says the vaccine also has an advantage in terms of side effects at a time when concerns about high fever and myocarditis, especially in young men, have put a damper on the COVID-19 vaccine campaign. Although no vaccine is said to be completely free of side effects, the vaccinia virus has been safely used in the smallpox vaccine for more than two centuries, and the vaccinia vaccine variant DIs used in the vaccine can no longer replicate in mammals. That means it is likely to cause far fewer side effects compared to other COVID-19 vaccines, he said.

A researcher is experimenting with the COVID-19 vaccine candidate developed by the Tokyo Metropolitan Institute of Medical Science.  |  THE TOKYO METROPOLITAN INSTITUTE OF MEDICIC SCIENCE
A researcher is experimenting with the COVID-19 vaccine candidate developed by the Tokyo Metropolitan Institute of Medical Science. | THE TOKYO METROPOLITAN INSTITUTE OF MEDICIC SCIENCE

Unlike AstraZeneca’s chimpanzee adenovirus vaccine vector, which was used in their COVID-19 shot, the vaccine developed by Kohara uses a smallpox vaccine strain that has already been used as a vaccine and whose efficacy and safety have been established as a vector, noted Tetsuo Nakayama, a project professor at the Kitasato Institute of Life Sciences and director of the Japanese Society of Clinical Virology. Nakayama is not involved in the development of the vaccine.

“Before the eradication of smallpox in 1980, the smallpox vaccine was used until 1976, and virtually all people born before 1976 have received it,” he said. “Although mice that received the smallpox vaccine have a confirmed immune effect, there may be a reduced immune effect in humans,” who received the smallpox vaccine.

Such concerns about reduced efficacy have also been raised for vaccines that use adenovirus as a vector to deliver genes or vaccine antigens, as experts say that previous vaccine recipients could have pre-existing immunity to the vector itself, which could reduce the vaccine’s effectiveness.

Kohara says he has found a solution to such concerns. Vaccines are typically administered into the muscle under the skin or in the subcutaneous fat. If the recipient received the vaccinia virus vaccine via these conventional methods, there has been evidence to show that a rarely used method of intradermal inoculation, a superficial injection just under the skin, would ensure the effectiveness of the vaccine without any problems, he said.

Laboratory tests have also confirmed the vaccine’s broad efficacy against coronavirus variants, including delta. While there were four different vaccines developed globally for different variants of avian flu, Kohara says that efficacy against all variants of coronavirus has been demonstrated from his individual vaccinia vaccine candidate. The vaccine is also likely to show efficacy against the omicron variant, he added.

Another advantage of the vaccine is its ability to be stored long-lasting in dried form at room temperature, which will be particularly beneficial for developing countries with tropical climates.

“The current situation is that we need to be vaccinated as often as every three or six months and we will have to make new vaccines every time new varieties of concern emerge,” he said. “So if the effectiveness of our vaccine lasted for just one year, two years or three years, it would translate into huge savings worth trillions of yen for the social infrastructure as a whole. The vaccine also has high cross-immunity to work against many variants, so these two things alone justify the manufacture of this vaccine. “

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