University of Hawaii professor leads campaign to create vaccine to protect against melioidosis

When Tung Hoang escaped war-torn Vietnam as a refugee in the late 1970s, not much was known about a mysterious disease that was killing his countrymen and hundreds of U.S. soldiers, enough so that it was called the Vietnam time bomb.

Today the University of Hawaii at Manoa professor is leading a campaign to create a vaccine to protect against melioidosis, now classified as one of the deadliest diseases in the world.

Hoang’s lab in Manoa’s School of Life Sciences was recently awarded a $3 million contract from the U.S. Department of Defense’s Defense Threat Reduction Agency to work on the project.

It’s serious business, because the disease has nearly a 50% mortality rate and is listed by the Centers for Disease Control and Prevention as a Tier 1 select agent, joining the likes of anthrax and Ebola because of its potential for use in the kind of bio-terrorism that could lead to mass casualties or severe threat to public health and safety.

The bacterium that causes the disease is endemic to Southeast Asia and Northern Australia and is commonly found in rice fields, polluted water and soil. People can become infected through cuts in their skin, by drinking contaminated water or inhaling particles that contain the bacterium.

Today the bug has been established in tropical areas around the globe, and one study estimated that about 165,000 people are infected by melioidosis per year, with tens of thousands dying.

One reason the death toll is so high is that the disease is notoriously misdiagnosed. It has a wide range of symptoms that can be mistaken for staph infections or diseases such as tuberculosis.

For Hoang, the work on the vaccine lands close to home.

Hoang and his dad were among the hundreds of thousands of Vietnam boat people who escaped their country by perilous sea journey following the end of the war. The Hoangs landed in a refugee camp in Thailand and were eventually sponsored for resettlement by a church near Calgary in 1981.

As an adult, the younger Hoang would return to Vietnam, and while visiting a relative, he walked into a rice field in his bare feet.

He didn’t know then just how risky that was, he said, but as a budding microbiologist he became increasingly interested in the disease and the bacterium that causes it.

“It’s there and it infects a lot of people,” he said. “I wanted to learn more, and I became passionate about it.”

Hoang’s UH lab began studying the Burkholderia pseudomallei around 2008. After much trial and error, the researchers developed the techniques to identify two specific surface proteins that allow the bacterium to attach to human cells for infection. Without the two proteins, the bacterium loses its power to infect.

The findings were released in a study published in the journal Nature Communications in March.

“Unlike most viruses, which have less than a dozen proteins, bacteria have thousands of different proteins,” Hoang said. “It’s like finding a needle in a haystack — finding which ones are important for infection and disease, and which ones can be used for an actual vaccine candidate.”

THE TWO proteins were used to create an initial vaccine and the study showed 100% effectiveness in mice. Unvaccinated mice died within five days, while all of the vaccinated mice survived.

Following the successful trial, they submitted an application to the Defense Threat Reduction Agency that was selected for funding.

Among the project’s goals is to provide protection from the disease for members of the military serving in tropical areas overseas, as well as for civilian travelers to endemic countries.

Hoang said the bio-terrorism potential is no joke.

“It’s not only deadly, it’s readily available. You can go to Asia and collect this thing, and it requires very little expertise,” he said. “You can culture microbes in high numbers and you can grow it overnight.”

Hoang said he’d love to knock Burkholderia pseudomallei off the CDC’s Tier 1 list.

“It would be good for humanity,” he said.

WITH HAWAII sitting about 20 degrees north of the equator, the islands are within the bacterium’s tropical range, making it a prime location for it to live or be transmitted to Hawaii from another country.

But while a few travelers from endemic countries have been detected with the disease in Hawaii, the bacterium itself has not been confirmed living on Oahu. And while a 1999 study found bacterium in the soil of a pasture on Hawaii island, the disease has not been a problem anywhere in the islands.

“I wonder if there’s a condition in the soil or a competing bacterium that make it unfavorable to exist here,” said Yun Heacock-Kang, a researcher also on the project.

Hoang and Heacock-Kang said the question might be worth exploring, but for now there’s no money to fund the research. Hoang said he also suspects the bacterium is still on the Big Island, but again there’s no funding.

Ian McMillan, UH Manoa microbiology Ph.D. graduate and co-researcher on the project, said there’s much more work to do before a vaccine emerges. with more trials and testing expected over a 5- to 10-year period.

“Perseverance in the lab is essential,” he said. “Failing is part of the process, but you can’t stop. You have to keep going. Hopefully we’ll end up in clinical trials.”