By Markian Hawryluk | The Bulletin

Grace Bio-Labs, a Bend-based life science research company, has received a federal contract to develop a screening tool that could help speed the development of a universal flu vaccine.

The company will produce a microscope slide printed with thousands of flu proteins, known as antigens, that will allow researchers to determine in a single test whether their vaccines produce antibodies to the various proteins. The 1-by-3-inch slide can be read by an imaging machine developed by the company, providing test results in mere seconds.

"You have all these antigens from people that have been put in a repository and are available all over the world," said Charles McGrath, founder and chief scientific officer of Grace Bio-Labs. "We select from that to put down the ones that are most likely to be important for the universal vaccine."

Researchers currently test blood samples for antibodies in batches of individual tests that are both time-­consuming and expensive to complete.

"We're surveying this comprehensive panel of antigens in one step, so you're getting a view of the full catalogue of what's represented in that sample and what it's reacting to," said Jennipher Grudzien, Grace Bio-Labs' president.

The Grace lab-on-a-chip could give researchers a quick screening tool to see to which antigens the antibodies produced by vaccine are binding.

"With binding antibodies, you have generated antibodies to areas of interest," said Dr. Pedro Piedra, a professor of molecular virology and microbiology at the Baylor College of Medicine.

"Then you have to determine later with a different system — if it's a vaccine you're looking at — to see what role it has in protection."

That could help researchers in their quest to find a flu vaccine that would protect against many, if not all, flu strains, and end the annual guessing game about what strains to include in the seasonal flu shot.

Each year, public health officials try to predict what strains will be circulating during the upcoming flu season, and manufacturers make vaccines to combat just three to four of those strains. In some years, that educated guess turns out better than in others, and the seasonal vaccine reduces the risk of infection by up to 60 percent. But in other years, those predictions miss their mark due to genetic changes in the flu viruses or because unexpected strains become dominant, dropping effectiveness as low as 10 percent.

While the seasonal flu vaccine offers better protection against infection than not being vaccinated, experts say the form of protection is less than ideal and well below the level of protection offered by other types of vaccines.

"The 2017 to 2018 influenza season in the United States was among the worst of the last decade and serves as a reminder of the urgent need for a more effective and broadly protective influenza vaccine," Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in May. "An effective universal influenza vaccine would lessen the public health burden of influenza, alleviate suffering and save lives."

A universal vaccine might also protect against flu pandemics, which occur when new influenza viruses in animals undergo genetic changes that allow them to infect humans, and to spread from human to human. That's what occurred in 2009 when the H1N1 virus spread from pigs to humans and caused a worldwide pandemic that killed more than 200,000 people. By the time the H1N1 vaccine was produced, the flu season was largely over.

"The concept of a universal flu vaccine is to have a vaccine that will protect you against any strain that might come through, so you didn't have to pivot all the time. And in addition, that would yield a vaccine that was also protective of such a strain that might cause a pandemic," said Dr. Bruce Gellin, president of global immunization for the Sabin Vaccine Institute. "It's been the holy grail of influenza for a long time."

He quoted Dr. Ed Marcuse, a University of Washington pediatrician and immunologist who famously said, "The pandemic clock is ticking; we just don't know what time it is."

"That is really the heart of the problem," Gellin said. "We don't know when, and we want to get as far in front of this with the science as possible."

The quest for a universal flu vaccine includes work to better understand how the immune system reacts to the influenza virus, and that could benefit seasonal vaccine design until a universal vaccine is ready.

Seasonal vaccines primarily target proteins on the head of the virus. But those proteins can vary greatly from strain to strain, and undergo genetic mutations that limit the vaccines' effectiveness. Researchers are now trying to develop flu vaccines that would target other areas of the virus, such as the stalk of the virus, that remain consistent from strain to strain. The Grace Bio-Labs microchip includes those proteins that remain consistent from strain to strain.

While researchers have a long way to go before a universal flu vaccine becomes a reality, there is growing optimism that such a vaccine is possible. In February, National Institute of Allergy and Infectious Diseases officials published a strategic plan for developing a universal flu vaccine, saying that scientific advances have made a universal vaccines "more feasible than a decade ago."

A Senate bill introduced in February would provide $1 million over five years to support research for a universal vaccine, and The Bill and Melinda Gates Foundation, along with Lucy and Larry Page, co-founder of Google, issued a $12 million challenge this year to encourage new players and promote innovation in the research for a universal flu vaccine.

One phase 3 trial currently underway is testing a vaccine candidate developed by Israeli biotech BiondVax Pharmaceuticals. Many researchers believe the road to a universal flu vaccine could involve a number of interim vaccines that go beyond the strain-specific, seasonal formulations to provide broader protection against a range of flu subtypes.

But Gellin said there is a complacency among the general public when it comes to the flu that researchers must guard against.

"They're tired of hearing about this. We heard about the pandemic, we heard about bird flu, we heard about 2009, and the world doesn't seem to have collapsed," he said. "There is still a need to answer big questions of science related to better understanding of influenza virus and influenza immunology if we're going to get anywhere."