Experts urge caution over 'escape mutations' found in coronavirus variants in Japan

TOKYO -- A series of coronavirus variants appearing to have an "escape mutation," which decreases the efficacy of immunity against the virus, have been found in and outside Japan.

According to Japan's National Institute of Infectious Diseases (NIID), "a rampant spread of the mutation within the country can pose risks for controlling infections in the mid- and long term," but does not make the vaccine ineffective at the present stage. This mutation differs from a new strain of the virus from Britain, which is said to be more transmissible than the original. What kind of risks can be feared from the "escape mutation"?

A mutation of a virus indicates a change in genetic information during the process of its multiplication. Although mutations are dependent on the scale of the virus' spread, in the case of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, it is believed to undergo mutation at a pace of around once every two weeks on average. Although it is rare for the characteristics of viruses to change greatly, there are cases where their properties alter when there is a change in amino acids constituting protein made from mutations.

The possibility of an escape mutation -- called this way to refer to dodging attacks of the immune system -- has been pointed out for a mutation called "E484K," where a change is seen in the 484th amino acid of the "spike protein" on the surface of the virus, which plays a great role in initiating infection.

According to the NIID, E484K mutations were found in 91 cases across east Japan's Kanto region, and in two cases during airport quarantine inspections, as of Feb. 2. Tokyo Medical and Dental University reportedly confirmed three cases of E484K mutations from test samples of patients who were hospitalized or visited the university hospital between late December 2020 and mid-January 2021. Furthermore, the Kobe Municipal Government in western Japan announced having found five instances of virus strains with a E484K mutation as of Feb. 18. These virus strains are believed to have been brought in to Japan from overseas.

Meanwhile, a team of researchers at Keio University that conducts analysis on genetic information, indicated the view that an E484K mutation possibly occurred in Japan in two virus samples collected in August and December 2020.

From the end of last year, global alarm has mounted over coronavirus variants originating in Britain, South Africa, and Brazil, which all have N501Y mutations with a replacement in the 501st amino acid of spike proteins, and are believed to be more transmissible than the original. Although the virus strains from South Africa and Brazil also have the E484K mutation, the N501Y mutation has not been confirmed in the coronavirus variant with the E484K mutation found in Japan.

When a virus enters the body, antibodies for attacking and eliminating it are made. In the case of the coronavirus, neutralizing antibodies that weaken the ability of spike proteins on the surface of viruses are said to be particularly effective for preventing infection.

Jun Ohashi, associate professor of population genetics at the University of Tokyo, said, "The 484th amino acid is the part where neutralizing antibodies cognize spike proteins on the surface of viruses. Therefore, it is possible that antibodies gained upon past infections with the coronavirus or vaccination will not be able to perform sufficiently against viruses with E484K mutations."

The NIID spoke of the possibility that "the status of the spread of the E484K mutation in Japan is being underestimated," and pointed out that beefing up the monitoring system for individuals entering the country as well as strengthening genome analysis are imperative to get a handle on the situation. The World Health Organization has expressed great concern regarding the E484K mutation, stating that it could potentially impact immunity that responds against foreign objects inside the body as well as the efficacy of vaccines. In practice, numerous overseas studies have shown findings that based on the level of experiments, the effectiveness of neutralizing antibodies gained after getting infected with the coronavirus or receiving developed vaccines is weaker against viruses with the E484K mutation.

However, U.S. pharmaceutical giant Pfizer and U.S. biotech company Moderna, which have developed messenger RNA (mRNA) vaccines, revealed respective trial results showing that the impact of mutations is small and that antibodies exceed the necessary level. Japan's NIID has also stated, "It can be thought that the E484K mutation alone is not something that will nullify the effectiveness of vaccines."

Tetsuo Nakayama, specially appointed clinical virology professor at Kitasato University, commented, "It is not the case that only antibodies eliminate viruses, and there is an immune response called cellular immunity where infected cells are directly attacked without involving antibodies. As mRNA vaccines can induce the activity of cellular immunity, a form of acquired immunity, even if the effectiveness of vaccines falls by a bit due to mutations, it's not that they don't work at all at the present stage."

The proportion of virus strains with a D614G mutation, which appears to be more transmissible than the original strain first found in Wuhan, China, has been on the rise around the world, including in Japan. Multiple variants including one with the N501Y mutation, which is said to be even more transmissible than the D614G, are also gradually increasing within Japan. The NIID said that moving forward, if strains with N501Y mutations spread further, "there is the risk that infections will spread more rapidly than the current state."

Hiroaki Takeuchi, virology lecturer at Tokyo Medical and Dental University, said, "During the current state where infections are continuously emerging, mutations will also happen at a greater frequency. As there is also the possibility that virus strains originating overseas, which are thought to have been increasingly found in community transmissions, will undergo further mutation to become more transmissible to Japanese people, taking thorough preventative measures against infection and decreasing the number of infections are more important than anything else."

(Japanese original by Ayumu Iwasaki, Science & Environment News Department)