Vaccination key to preventing variants

Variants of the novel coronavirus are surging. The so-called British variant of COVID-19, which has spread across the world, is reported to be more infectious than the original strain.

In Japan, confirmed cases of COVID-19 variants have been increasing particularly in the Kansai region. They now are thought to have almost replaced the original strain across Japan. Variants tend to make even young people without underlying medical conditions vulnerable to serious illness, overwhelming hospitals in the prefectures of Kyoto, Osaka and Kobe.

In April, the government declared a third state of emergency in Tokyo as well as Osaka, Kyoto and Hyogo prefectures, but the pace of decline in infections has been slower compared with the previous two states of emergency. Even when it becomes possible to lift the latest state of emergency after successfully holding down infections, the flow of people will return to normal levels, making it more likely that a situation will reemerge in which infections will spike, leaving hospitals struggling further to find beds for newly infected patients.

With the original coronavirus strain, Japan has managed to keep COVID-19 infections and deaths at low levels despite far more moderate preventive measures than those taken in Europe and the United States. In other words, what I call Factor X, a yet-to-be-defined element, saved Japan.

Unfortunately, it seems that Factor X is no longer effective to abate variants of the virus. Therefore, Japan now has to deal with its most serious predicament since the novel coronavirus epidemic was first reported in China 1½ years ago.

Fortunately, COVID-19 vaccines have been developed at a much faster speed than anticipated by most scientists. They also are more effective than expected. The Pfizer vaccine, which is already being rolled out in Japan, and the Moderna vaccine, whose use in Japan will begin soon, are so similar to each other that they can be referred to as twins. The two U.S. firms utilize Dr. Katalin Kariko’s patent on messenger RNA (mRNA) technology to produce vaccines by synthetically producing as their main ingredient part of the genetic material of the coronavirus.

Clinical trials involving tens of thousands of people showed the efficacy rates were 95% for Pfizer and 94.1% for Moderna.

It’s become known that the percentage of vaccinated people who develop adverse effects such as fever and fatigue is in double digits, but that such cases go away within a few days on their own. The proportion of vaccinated people who experience severe allergic reactions such as anaphylaxis ranges from one in tens of thousands to one in hundreds of thousands, but there are established treatments for this.

COVID-19 vaccines are reported to be as effective against the variants of the virus that are raging in Japan as they are against the original strain. There was an explosive increase in infections and deaths in Britain and Israel caused by the British variant from late December to early this year, and those countries launched campaigns to vaccinate as many people as possible. As a result, they have succeeded in curbing coronavirus infections. Likewise, the United States, which still has the largest number of cumulative cases, is seeing a rapid drop in new cases, to the extent that it is now resuming economic and social activities.

It is no exaggeration to say that the fate of Japan hinges on whether it will be able to successfully implement widespread vaccination against COVID-19.

To enable as many people as possible to get jabs, it is indispensable to secure sufficient vaccine supplies and prepare logistics and infrastructure for nationwide vaccination. The government says it has secured enough vaccines to administer two doses to the entire population. Following the government’s instructions, each municipality is now doing its best to implement across-the-board, on-site vaccination programs. Dentists have expressed their readiness to help doctors and nurses administer vaccine shots.

So far, there have been conflicts of opinion in Japan over what should be done to contain the COVID-19 pandemic. But I now am looking forward to seeing the government and the people join hands to expedite the nationwide vaccination drive.

As in the past, when the Japanese population worked together to overcome the tribulations of the post-World War II period and numerous natural disasters, we now have to be united to weather the ongoing national crisis.

For smooth implementation of the COVID-19 inoculation program, there are some challenges to be resolved, apart from securing vaccine supplies and preparing vaccination infrastructure.

What proportion of the Japanese population wants to be vaccinated? This is the first thing we need to know. With more than half of their populations having already received at least one vaccine dose, both Israel and Britain are now seeing their daily per-capita cases falling below those in Japan day after day. The share of the population vaccinated against COVID-19 should preferably be as high as possible to make the nationwide inoculation program effective in ending the pandemic. Nevertheless, part of Japanese society remains strongly skeptical of vaccination. Thus, measures to raise the vaccination rate to a substantially high level are critical for Japan to bring an end to the pandemic nationwide.

The second challenge is to know how long people receiving vaccine jabs remain immune to COVID-19. The length of the immunity people gain in the wake of infection or thanks to vaccination varies depending on the virus. Immunity to measles and rubella lasts several decades following infection, but immunity to COVID-19 is reported to wane months after infection.

Although the efficacy of the Moderna vaccine gradually weakens as time goes by, it is reported to offer sufficient protection against COVID-19 even six months after vaccination. However, whether the immune response continues beyond that period remains unknown.

The COVID Vaccination Record Card prepared by the U.S. Centers for Disease Control and Prevention has four areas for recording vaccine doses, apparently indicating that the agency anticipates the need to give Americans another round of jabs in the near future. Japan also needs to work out a long-term vaccination program in preparation for additional inoculation campaigns.

The third challenge is how to deal with variants of the virus. The Pfizer and Moderna vaccines are reported to be likely to be highly effective against coronavirus variants first identified in Britain, South Africa and Brazil — which are among the COVID-19 variants on the watchlists of the World Health Organization and various countries.

However, it remains unknown if these vaccines also can be effective against the variant that has been spreading in India. Even in Britain, which has carried out one of the fastest vaccination campaigns in the world, there now is a gradual increase in the number of cases of the Indian variant of COVID-19, prompting the country to be on its guard against it.

In countries that are rapidly allowing vaccinated people to resume activities without wearing masks or social distancing, there still is concern about the emergence of new variants of the virus that resist the vaccine.

The advantage of the method both Pfizer and Moderna use for COVID-19 vaccine production is that it allows them to swiftly develop new vaccines that can be effective against coronavirus variants. But we need to keep in mind the possibility of encountering a vicious circle of the appearance of one variant after another and further vaccine development. This means that a long-term vaccination program is essential to cope with variants.

As a person engaging in medical research in Japan, I feel ashamed that our country cannot demonstrate its presence in the area of COVID-19 vaccine development.

Katalin Kariko, who pioneered the mRNA technology as early as in 2008, was initially unable to receive U.S. federal government research grants, eventually even facing demotion at her university. Nonetheless, she tenaciously continued her research and development efforts, ultimately leading to the development of the breakthrough COVID-19 vaccines.

After receiving patent licenses from Kariko, Pfizer and Moderna launched a project to develop mRNA-based vaccines in January 2020. After a short while, in the summer of last year, clinical trial results for a vaccine candidate were published to announce that its administered dose produced dose-dependent immunogenicity in all of a small cohort of volunteers, numbering in double digits, in early-phase trials.

The publication prompted the United States and European countries to provide massive research grants to vaccine development projects, with tens of thousands of people volunteering to take part in large-scale clinical trials. The prompt release to the public of epoch-making data turned out to be a conduit to abundant research investment, clearly encouraging many people involved in vaccine development.

In Japan, small-scale clinical trials of COVID-19 vaccine candidates are underway. I look forward to seeing promising peer-reviewed data from their trials published in a journal as early as possible.

Shinya Yamanaka

Yamanaka was born in Osaka Prefecture in 1962 and graduated from the School of Medicine, Kobe University. He is the director of Kyoto University’s Center for iPS Cell Research and Application (CiRA), a post he has held since 2010. He won the 2012 Nobel Prize in Physiology or Medicine for producing induced pluripotent stem (iPS) cells.