BY OSAMU TSUKIMORI
At present, big-name pharmaceutical and biotechnology firms around the globe are in an intense race to develop the world’s first vaccine for the novel coronavirus which would potentially lead to national bragging rights and huge profits for successful companies as countries hope to put their economy back on track earlier than other nations.
A total of 142 vaccines were being developed as of Monday, of which 13 are were clinical evaluation, according to the World Health Organization. British drugmaker AstraZeneca PLC and U.S. biotech firm Moderna Inc. are considered two of the leading candidates to put the world’s first vaccine on the market as early as by the end of this year. At home, AnGes Inc., which has teamed up with Takara Bio Inc. and Osaka University, is considered the front-runner, aiming to launch the vaccine as early as next spring, followed closely by Shionogi & Co. among other domestic efforts.
But at the same time, questions arise. Is there a possibility that the safety or efficacy of the vaccine may be overlooked so as to prioritize the speed of the development? If Japan is lagging behind other countries in vaccine development, how would that affect the country when it tries to import them?
Dr. Tetsuo Nakayama, a project professor at Kitasato Institute for Life Sciences and director of the Japanese Society of Clinical Virology, spoke to The Japan Times to help shed some light on the current development of vaccines at home and abroad and the risk of the heated competition.
Which companies are leading the global race in developing the vaccine?
U.S. firm Moderna looks to be making the most progress.
It has announced its messenger RNA vaccine has generated antibodies in people in a phase one trial (designed to assess its safety and tolerance), but there’s no detailed data to show that it would protect them against infection.
Simply put, an influenza shot injects a protein into the body. Messenger RNA and DNA vaccines, meanwhile, force production of proteins that resemble the pathogen, so in that sense the most we can expect may be about the same as the influenza vaccine in terms of reducing the most severe effects of the disease, and it may not have the ability to put the disease under control.
The most important thing is whether the use of DNA or messenger RNA vaccines stimulate the production of protective neutralizing antibodies and induce the cellular immune response. At this point, it remains unclear whether the DNA vaccine under development by AnGes or messenger RNA vaccine by Moderna would induce the cellular immune response.
But in a worst-case scenario, some antibodies may worsen the disease by essentially helping increase the virus inside the cell in a phenomenon called antibody dependent enhancement (ADE).
We don’t know whether there are concerns for ADE at this point after (getting the vaccine and being) infected with the novel coronavirus.
There are lots of unknowns, but I don’t think the vaccine would be ready by the end of the year. Osaka University has been working with Takara Bio Inc. and AnGes Inc. on a DNA vaccine similar to messenger RNA.
So is ADE a cause for concern for the general public?
If the vaccine is only to curb the occurrence of severe symptoms, the subjects for vaccination would likely be limited to older people or people with pre-existing conditions, and it’s too early to tell whether it’s a vaccine to be administered to children or adults in general.
Are there promising vaccine candidates worldwide?
There are two objectives of vaccines.
One is to prevent infection and another is aimed at not necessarily protecting against the disease but preventing severe symptoms.
Everybody is talking about developing a vaccine to halt the spread of infections, but that’s not something that can typically be achieved without a live vaccine. For example, the measles vaccine is a live vaccine, curbs the infection and prevents the risk of a serious disease for people.
But influenza, like the coronavirus, causes a respiratory tract infection, so it’s difficult to prevent the infection via vaccination through intramuscular injection. The vaccines under development could be similar in terms of efficacy to the influenza vaccine.
The West and China are leading the vaccine development. Will there be a delay for Japan to introduce the vaccines to its own people?
Yes, I acknowledge that there’s going to be a delay because those countries would prioritize the vaccinations of their own people.
I have seen no reports that the Japanese government has been providing funds to overseas manufacturers of vaccines, though the Trump administration in the U.S. has been funding various projects overseas to secure vaccinations for its citizens in case the domestic efforts fall through.
The European Union and the U.S. have the Mutual Recognition Agreement, which allows the drugs to be used within each other’s borders by avoiding the duplication of clinical trials.
But Japan still requires additional clinical trials, making it one of the very few jurisdictions that still requires that in the world.
During the swine influenza pandemic in 2009, Japan imported vaccines, but by the time Japan finished clinical trials on the imported vaccines, Japanese manufacturers had already supplied tens of millions of domestically produced vaccines and the epidemic was over, so the vast majority of the imported vaccines were not used in the end.
Is it possible that the same thing could happen this time around?
It’s hard to say for certain. But Japan has to undergo an additional clinical trial even if it wants to import a vaccine that has cleared regulatory approval overseas. So, under current rules, there’s going to be a delay.
Japan approved remdesivir for treatment of severe COVID-19 cases last month, soon after it gained approval from the U.S. Food and Drug Administration. So it will be different when Japan imports a vaccine made overseas, won’t it?
That is because dozens of clinical trials on remdesivir had been conducted in Japan.
It doesn’t mean that Japan does not have to go through a trial. But while we’re waiting for Japanese approval to be able to use the overseas vaccines, Japanese manufacturers should start producing home-made vaccines.
I have often said this, but a vaccine is a weapon to protect one’s own citizens, so we should not rely on overseas manufacturers.
Because people can get re-infected with the virus, is the vaccination essential for the general public?
It’s the same thing with influenza. You can contract it many times.
Because the novel coronavirus is also a respiratory tract infection, normally a vaccination would not protect against infection itself. So even if a person contracts the virus, it doesn’t necessarily mean that the person doesn’t get infected again.
So in a nutshell, are people supposed to take the vaccination every year, for instance?
We still don’t know that for sure if that’s going to be necessary if the novel coronavirus keeps changing its genetic mutations.
There are different types of the coronavirus confirmed across the globe. If a person gets vaccinated, does the person have an antibody against all types?
The person would have some degree of protection but it’s still too early to tell whether the vaccination would create cross-reactive antibodies in different subtypes of the virus.
With maybe too much focus globally on developing the vaccine as soon as possible, are there concerns that important issues like the vaccine’s efficacy, safety or side effects could be neglected?
Yes, those concerns are real, as we’ve seen a lot of failures in the vaccine development in the past. For example, a dengue fever vaccine made by Sanofi and based on a yellow fever vaccine embedded with the dengue virus appeared to be effective, but it caused the deaths of children who had been given the vaccination due to the phenomenon called ADE, explained earlier. There are always safety concerns, so the vaccination development must be conducted cautiously.
Are there concerns that Japanese vaccine manufacturers would turn a blind eye to certain aspects of safety, efficacy and side effects?
No. Japanese people are very sensitive and particular about adverse reactions such as fever or local reactions, so Japanese vaccines are among the best in the world and are considered extremely safe.
How long do you expect it to take for the vaccines to be available for all the general public?
I would expect as early as next year, but it would depend on the production capacity.