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[EYE] Developing cholera vaccine in South Korea

IVI director general Jerome Kim shares stories behind Euvichol, Korea’s first oral cholera vaccine

One of the most feared infectious diseases in 19th century Korea was inarguably cholera. The first outbreak of the acute diarrheal disease took place on the peninsula in 1821, after the virus spread from India to China’s Qing Dynasty. 

It is believed the disease killed more than 200,000 in two years starting from 1821. In 1859, another cholera outbreak occurred. This time, some 400,000 people in Korea -- about 50 percent of the entire population at the time -- were killed by the disease. 

It’s no surprise that the people of the Joseon era called the disease “hoyeolja,” which roughly translates to “a disease as painful as being ripped up by a tiger.”

More than 150 years later, the disease is no longer present in South Korea. The country, however, recently welcomed its first oral cholera vaccine Euvichol -- specifically developed for use in developing countries.

The development of the vaccine was the product of a five-year joint effort by South Korean firm EuBiologics and Seoul-based International Vaccine Institute. The Korean vaccine producer has been prequalified by the World Health Organization, meaning Euvichol has met acceptable standards of quality, safety and efficacy to be purchased by countries and international agencies such as UNICEF.

Jerome Kim, director general of IVI, said the development of Euvichol is especially meaningful, as oral cholera vaccine production has been globally low with demand exceeding supply. Last year, the Nepal alone requested 450,000 doses of the vaccine in order to prevent cholera after the devastating April earthquake that killed over 8,000 people. 

“There was endemic cholera in Nepal and there was a big fear that there could be an outbreak after the earthquake,” Kim said in an interview with The Korea Herald. 

“And the Korean government actually said it would fund vaccinations, but there wasn’t sufficient cholera vaccine in the stockpile.” 

Sudan and Haiti last year also made requests to WHO for supplies of cholera vaccines to conduct preemptive vaccination campaigns, but there was a global shortage, according to the agency. 

WHO explains that the additional capacity (of Euvichol) contributes to reversing a vicious cycle of low demand, low production, high price and inequitable distribution, to a virtuous cycle of increased demand, increased production, reduced price and greater equity of access. The addition of another prequalified cholera vaccine producer is expected to double global supply of oral cholera vaccine to 6 million doses this year, according to the agency.

While cholera is endemic in more than 50 countries, it doesn’t get attention except during humanitarian emergencies -- such as the outbreak among refugees in Goma, Congo, in 1994 that killed tens of thousands.

Based in Asia, IVI has been concentrating on developing vaccines for diseases that are common in less developed Asian countries, including cholera, typhoid and shigellosis. With a grant from the Bill & Melinda Gates Foundation and support from the South Korean government, IVI has been collaborating with a number of Korean firms, including SK Chemicals and EuBiologics to come up with affordable vaccines for global health purposes. Euvichol is one of the first two low-cost oral cholera vaccines produced by IVI, after a product called Shanchol. 

Accordingly, EuBiologics is the second low-cost cholera vaccine producer in the world. Euvichol -- a bivalent vaccine that offers protection from different cholera strains without a buffer -- is scheduled to be supplied for less than a dollar a dose through mass production. The buffer-free, inexpensive vaccine is expected to enable greater access to the vaccine in countries with limited resources. 

“What the laboratories at IVI did was that they determined that optical growth conditions for this particular vaccine, so they can make as much of it as possible and as cheaply as possible -- and in a manner that was reproducible. We actually had to develop a new series of standards and tests to reproduce the vaccine at a high quality.”

The vaccine will also be sold in lightweight plastic tubes that are much easier to transport than the glass vials that are currently being used, starting from next year. 

“Right now vaccines come in a glass vial with a rubber stopper and an aluminum top. To use the vaccine, you have to shake it and then you have to rip off the aluminum top -- it’s not like a can top that pops open, you actually have to grab it with your fingernail, lift it up and take it off. It’s kind of sharp so after the first 100 or so, your fingers hurt,” Kim explained. 

“So people have to use a surgical clip to pull it off and it takes a long time. However, the new version of EuBiologics uses a little plastic tube with a twist top. You can only put so many glass vials in a box, but with a plastic tube, you can throw them in and they’ll stack up and will be relatively flat. So you can pack a lot more, more cheaply and more quickly. And that’s much easier to use because you just have to twist off the top.”

Cholera, a potentially fatal infectious disease that causes acute watery diarrhea, has affected vulnerable populations for centuries. It is most likely to be found and spread in places with inadequate water treatment, poor sanitation and inadequate hygiene. 

And that is why some countries keep their cholera outbreaks a secret, as they fear bad publicity, and it’s a concerning issue, Kim said. According to WHO, about 1.4 million to 4.3 million cholera cases occur worldwide annually, and as many as 142,000 people die from the disease each year. 

“There were a number of (cholera) outbreaks last year that didn’t get reported,” Kim said. “In fact, some countries don’t report any cholera at all, even though we know there is cholera because we test vaccines there. Cholera carries a very negative connotation of failure and unhygienic conditions. It traditionally has been associated with bad publicity. Countries do not talk about it so they don’t lose tourism or business continues as usual. And it’s a big problem.” 

Developing vaccines poses a number of unique challenges, including working with different governments and getting their approval for clinical trials. As cholera doesn’t have the potential to be a problem in South Korea, trials for Euvichol in fact took place in the Philippines. Clinical trials for Shanchol, another oral cholera vaccine based on a vaccine technology developed by IVI, were done in India. “Sometimes the regulatory authorities throw a curveball at us. We don’t know what to expect until we actually do the submission,” Kim said. 

“But (IVI understands) someone in the country has to be responsible for the testing and development of vaccines and drugs. And it’s a huge responsibility.” 

Kim previously served as principal deputy and chief at the Laboratory of Molecular Virology and Pathogenesis at the U.S. Military HIV Research Program. His research interests include HIV vaccine development and HIV molecular epidemiology. 

He said IVI is interested in developing vaccines for HIV, adding that the HIV epidemic has resurged especially in young gay men aged 18-30 in Asia, as well as in North America. 

“If we look in Thailand, the incidence is 10 percent -- that is 10 new infections per 100 young men per year,” he said. 

“If you look in China, same thing. And if you look in Japan, same thing. It’s really a problem throughout the region. And it’s been a very difficult epidemic to control. Thailand made a tremendous turnaround in HIV prevention in the 1990s. They haven’t been able to do that in homosexual men because it’s difficult to reach that population.”

By Claire Lee (