Each year, influenza viruses bring aches, pains, fever and overall misery to millions of people. The flu also leads to hundreds of thousands of hospitalizations and thousands of deaths.
In a new paper published in Genome Medicine, researchers say a blood test may be able to identify which people are more likely to fight off the flu and which may have a harder time. And information from that same test could lead to new treatments — including more effective vaccines — that might make more people more flu-resistant.
For four years, Purvesh Khatri, an associate professor of medicine and biomedical data science at Stanford University, and his colleagues have been parsing the immune system for clues about how best to ward off the flu virus. When they scanned the entire human genome for the genes that might be protective, they came up empty. So they decided to focus on the cells that made the most sense in their search — the immune cells whose job is to fight incoming microbes like influenza.
They recruited 52 people who had their immune systems analyzed and then volunteered to inhale flu viruses to see if they became infected. The researchers learned that the people who experienced the worst flu symptoms had lower levels of certain kinds of immune cells known as natural killer cells, while those who didn’t get as sick seemed to have higher levels of these cells.
Khatri and his team traced the natural killer cells back to the gene that codes them, and the protein called CD94 that the gene produces. The more CD94 people have in their blood, the milder their flu, while people with lower levels of CD94 seemed to experience worse symptoms.
“The reason we are excited is because until now, we didn’t know where to look [for ways to protect against flu],” he says. “We now know where to look.”
Knowing how some people might be better equipped to fight off flu could also lead to better vaccines or treatments that give that same protection to others. Because higher levels of natural killer cells seem to indicate a general heightened level of immune alertness, they’re more likely to mount an effective defense against flu. That could provide the foundation for a more effective universal flu vaccine, for example, that triggers a stronger immune response than current vaccines, which to match whichever strains of influenza are circulating at the time.
“Until now we have been focused on creating vaccines that give [specific] immune responses. But this finding means that even before that virus is recognized by any immune cells, the baseline immune status of the natural killer cells seem to be a major player in deciding if somebody becomes infected or not. So now the question becomes whether we can design a vaccine that can move people toward this higher baseline status where they have a slightly higher proportion of natural killer cells,” says Khatri. A vaccine based on the idea of bringing the overall immune system to a higher state of readiness to counter any viruses it encounters, including a range of flu viruses, could help more people fight infection.
It wouldn’t take much, according to these early study results. People in the study who seemed to experience fewer flu symptoms had about 10% to 13% of their immune cells made up of natural killer cells, while those who had the worst symptoms had less than 10% of natural killer cells.
But while having a higher proportion of primed killer cells may be good for fighting the flu, it is still not known whether it could have negative health effects as well. Overactive immune responses can be deadly, resulting in a storm of inflammation in which immune cells go rogue and begin destroying healthy tissues and cells. Heightened immune responses are also responsible for debilitating autoimmune diseases, in which immune cells mistakenly target the body’s own cells as potential invaders like bacteria or viruses. “The big unknown is what the downside could be,” says Khatri.
But the results, while preliminary and only in a limited number of people, are an important first step in identifying natural killer cells as a possible new target in fighting flu. In recent years, manipulating the immune system has provided new and effective ways of treating cancer, and he anticipates some of the lessons learned from the cancer world might apply to make flu treatments more effective as well.