Lagging in vaccine race, research environment blamed

As European countries, the United States and China announce regulatory approval for new COVID-19 vaccines and many countries begin mass vaccinations, their swift progress in vaccine development has served to highlight delays in developing a home-grown vaccine in Japan.

To be lagging internationally in this area poses risks, experts say, as new infectious diseases become potential global threats and new pandemics are likely to emerge in future. But these experts say years of underfunding science research in general has hampered vaccine efforts, despite several Japanese scientists being awarded Nobel prizes in science in recent years.

Last September, as the virus raged across the globe, Japan adopted an emergency budget of JPY48. 5 billion (US$466 million) aimed at COVID-19 vaccine development.

Osaka University medical school was given JPY11 billion (US$106 million) from the emergency budget and currently leads Japan’s first clinical trials for a new DNA vaccine under AnGes, its drug development venture with Takara Bio Inc, a leading pharmaceutical company.

Other COVID-19 vaccine candidates under development in Japan have yet to reach the clinical stage. Japanese pharmaceutical firms KM Biologics, part of Meiji Holdings, and Daiichi Sankyo are planning to launch clinical trials of their vaccine candidate in March, most likely outside Japan in other Asian countries.

Ryuichi Morishita, a gene therapy professor at Osaka University who founded AnGes, called for a better framework to support rapid vaccine development in Japan. “Japan lacks the capability to respond to a pandemic quickly,” he told Nikkei media in October 2020, admitting it would be difficult to develop a marketable vaccine by the end of 2021.

Research environment problems

Japan does not lack vaccine development capability. However, “Japanese researchers are frustrated because of low funding and a lack of support from the government for innovative research. As a result, Japan has fallen behind in the global competition,” said Haruka Sakamoto, researcher in public health at the department of global health policy, University of Tokyo.

“[The drawback of] researchers facing poor access to stable funding has affected vaccine development, which is costly and involves many risks of failure,” explained Sakamoto.

According to experts, Japan’s decline in scientific research can be traced to government policies such as the landmark university reform regulations enacted in 2004. Facing a loss in national revenue, the government changed the status of national universities into corporate entities. The reform involved an overall drop of 1% annually in funding from the government, forcing universities to face up to less spending and decreasing public subsidies for research.

They link this to a decline in international rankings, especially in terms of papers published by Japanese researchers.

For example, last December, the Japan Science and Technology Agency reported that Japan was in 16th place internationally, with 947 peer-reviewed COVID-19 papers published. In contrast, the United States topped the list with 15,622 papers, followed by China, the United Kingdom and Italy.

Researchers also cited lower globalisation in Japan, pointing to US company Pfizer’s development of Germany-based BioNTech vaccine, and Bio Farma in Indonesia’s agreement to manufacture a vaccine developed with China’s Sinovac Biotech after large-scale collaborative clinical trials – although efficacy results are still disputed.

Low infection rate hampered vaccine development

Tetsuo Nakayama, a project professor at Kitasato Institute for Life Sciences in Tokyo, contends that low infection rates domestically is another reason for slow vaccine development.

Although China also saw low rates of infection after May 2020, clinical trials of Chinese vaccines were conducted in countries with much larger caseloads, notably Brazil, Indonesia and countries in the Middle East. The UK’s AstraZeneca conducted trials in India and South Africa.

“The negative impact of focusing only on Japan by researchers was seen during the rise of the SARS and Ebola viruses. Both these diseases did not affect Japan badly which meant it was hard for Japanese researchers to conduct large human clinical trials and that meant they found it harder to access funds to support their research,” explained Nakayama, who is also director of the Japanese Society of Clinical Virology.

He added that the unprecedented fast commercial development of vaccines by foreign companies is based on years of past research in less stressful times. “That research approach is almost abandoned in Japan, and that is dangerous,” he said, referring to the need to prepare for future pandemics.

Sakamoto also pointed to past problems with vaccine development as another dampener for Japanese research. In the 1990s the government discontinued a local MMR (measles, mumps and rubella) inoculation campaign after cases of aseptic meningitis were reported, even though no definite link was proven.

Focus on side effects

Experts now say ongoing COVID-19 vaccine development in Japan will need to focus on tackling issues that have emerged with ongoing inoculation programmes.

“Japanese research in the long run will contribute to improvements in areas such as allergic after-effects now being observed with some of the approved vaccines, and better storage,” explained Nakayama, pointing to the need for hyper-cold storage of the Pfizer-BioNTech vaccine, which was the first in the world to be approved and rolled out in the United Kingdom after being approved by the UK medicines agency in early December.

Japan is currently in its second emergency state, recording on average more than 2,000 new COVID-19 infections a day across the country. In the absence of a locally produced vaccine, Prime Minister Yoshihide Suga has pledged to secure vaccine doses for 60 million people from US pharmaceutical company Pfizer and two other European counterparts.

This week Suga also agreed on a programme with philanthropist Bill Gates to distribute coronavirus vaccines to developing countries to ensure the safety of the summer Tokyo Olympics, postponed from last year.