“There is concern about the safety of vaccines in Japan”

The year of the vaccine

European and Japanese involvement in developing inoculations for Covid-19


JANUARY 2021 Feature / Text by Gavin Blair

One bright spot during the global pandemic has been the development and approval of multiple vaccines against Covid-19 — all in under a year. To put this in perspective, the average time it takes to create vaccines is 10 years. The Pfizer–BioNTech, AstraZeneca–Oxford, and Moderna vaccines, along with China’s SinoVac and Russia’s Sputnik, are already being administered. There are also dozens of other vaccines at trial stages around the world, including two from Japanese companies.

The speed of Covid-19 vaccine R&D has been possible due to reliance on existing technologies, massive government funding, and the relentless work of researchers. The Pfizer–BioNTech and Moderna vaccines both utilise messenger RNA (mRNA), which inserts a tiny piece of genetic code into cells that act as instructions to fight or prevent diseases. A pioneer of this research was Katalin Karikó, a Hungarian scientist working in the US in the 1990s. Karikó struggled with the problem of the body’s immune system attacking synthetic RNA, was unable to secure funding for her research, and was demoted at her university. In 2005, papers she co-authored suggesting this obstacle could be overcome caught the eye of the scientists who would go on to found BioNTech and Moderna.

The mRNA vaccines developed by the two companies involve a simpler manufacturing process than regular inoculations. The injected genetic code stimulates the body to make the viral proteins that will fight the infection, rather than including the proteins themselves in the injection. This also means the process of creating new versions of a vaccine to fight mutated strains is much faster.

“We knew that this virus mutates and there will be new strains coming up … we have the ability to create a re-engineered vaccine and make it available within six weeks,” Ugur Sahin, co-founder and CEO of Germany-headquartered BioNTech, told a JP Morgan healthcare conference this month. “This is one of the key advantages of messenger RNA.”

The biggest downside of mRNA vaccines is their instability — they break apart if they are not kept at very low temperatures. The Pfizer–BioNTech vaccine needs to be kept at -70°C degrees and its Moderna counterpart at -20°C.

The Jenner Institute at Oxford University had spent years working on vaccines for other coronaviruses — SARS and MERS — and had developed a platform to create inoculations against ‘Disease X’ in the event of an outbreak of a new virus strain. The Covid-19 vaccine developed by the Oxford team and licensed by AstraZeneca is an injection of the spike protein from the surface of the coronavirus. This causes the immune system to produce antibodies and activate T-cells to fight the infection. The vaccine can be stored in a regular refrigerator and costs approximately a fifth of the Pfizer-BioNTech inoculation and an eighth of the Moderna one.

In Japan, pharma firm Shionogi & Co. is collaborating with the National Institute of Infectious Diseases and Kyoto University on a vaccine and hopes to deliver enough doses for more than 30 million people by the end of 2021.

“We began a domestic phase one clinical trial in December,” says a spokesperson from the firm’s Osaka headquarters. “At this point, it is not possible to say when the vaccine will be available. There will be phase two and phase three trials and then the approval process … With infections rising as they are, we are working as quickly as possible but, of course, safety is crucial, as well as speed.”

On why vaccine development in Japan is behind the curve, the spokesperson says, “The Pfizer and Moderna vaccines are based on mRNA. This is a new technology and the level of knowledge about it is high among researchers in Europe and the US. But not in Japan. So, the starting point for coronavirus vaccine development was different. Put simply, that is probably the biggest reason development has been slower in Japan.”

A potential barrier to ending the pandemic is reluctance to receive a Covid-19 vaccine. In a survey commissioned by the World Economic Forum, this sentiment was shown to have grown in 10 of 15 countries between August and October last year. The number of those willing to receive a vaccine fell below 70% in the US, Spain, Italy, Germany, and Japan, and to only 54% in France. Many experts believe that 70% of a population needs to be vaccinated to achieve herd immunity, though estimates vary.

Some of the wariness around vaccinations in Japan stems from the country’s experience with the human papillomavirus (HPV), which can lead to cervical cancer. The immunisation rate among teenage girls was around 70% shortly after a vaccination programme was launched in 2009. However, following misinformed media reports of side effects, including muscle pain, sleep disorders, and light and sound sensitivity, the health ministry withdrew its recommendation for the vaccine in June 2013. HPV vaccination rates have since fallen to around 1% and studies suggest that this is leading to thousands of preventable deaths every year.

“There is concern about the safety of vaccines in Japan because of the history of the vaccination for human papillomavirus,” says Dr Kazuhiro Tateda, a professor at Toho University’s Department of Microbiology and Infectious Diseases.

Another worry is the danger of antibody-dependent enhancement. This is a rare and little understood reaction to some vaccines that causes a misfiring of the immune system, making people more susceptible to the disease they are being inoculated against.

“There have been cases of it with the dengue fever vaccine and nobody knows yet if it can happen with coronavirus vaccines. Many people in the medical profession [in Japan] are concerned about this,” says Tateda, who is also the president of the Japanese Association for Infectious Diseases and a member of Japanese government advisory panels on Covid-19.

One unknown with Covid-19 vaccines is how long they will inoculate against the disease for. It may be that an annual vaccination, like a flu jab, will be necessary until Covid-19 is eradicated, in the way smallpox was, by an inoculation developed by Edward Jenner, after whom the institute at Oxford is named. •