Can immune memory protect us from the flu?
By Erin Howe
It’s been about 80 years since the first flu shot was developed and since then, researchers have been searching for more powerful and effective vaccines. Vaccines, a mighty tool for preventing or mitigating illness from the flu, are particularly valuable when they’re well matched to the flu strains that circulate the season they’re administered.
But what if instead of being able to defend people against three or four strains of influenza, a vaccine could provide broad protection from all strains of the virus?
Researchers at the Temerty Faculty of Medicine are exploring whether the key to creating a universal flu vaccine could be immune memory; that is, boosting the body’s ability to recognize bugs it has fought before and arming the immune system with stronger tools and sharper surveillance.
Infection Prevention and Control Canada estimates that influenza kills about 3,500 people annually, making the flu one of the country’s top-10 causes of death. According to WHO, about 290,000 to 650,000 people around the world die from flu viruses each year. White blood cells called “T-cells” and “B-cells” are key players in keeping infectious invaders from wreaking havoc on our health.
Viruses like the flu contain antigens that can be recognized by the body’s immune system. When we encounter these micro-organisms, our B-cells make antibodies, the proteins that help fight off infection. The antibodies bind onto the antigens; if they can do this in a way that prevents the antigens from attaching to the cells, they can completely block infection.
They also call in reinforcements from other immune cells to neutralize the micro-organism. At the same time, T-cells recognize the influenza antigens hidden inside the infected cells and kill the infected cells to limit the spread of infection. After completing this mission, B-cells and T-cells remember their enemies, such as influenza, and are ready to battle them again in the future. Many vaccines work by stimulating an antibody response — courtesy of B-cells — to a virus. But like a shapeshifter, influenza mutates quickly to evade even the strongest antibodies. T-cells, however, recognize viruses no matter how they may change. Within a few days of spotting their foe, T-cells spring into action to multiply and knock out infection. As they eliminate their enemy, T-cells ramp back down again. The T-cells that are left over when the immune system returns to baseline are memory T-cells, or lymphocytes. When the surviving lymphocytes see an intruder like the ones they’ve defeated before, they know what to do to knock it out.
Karen Yeung, a PhD student in Temerty Medicine’s Department of Immunology, is exploring how a type of lymphocyte called CD8 T-cells — or killer T-cells — can persist to clear infenction.
“It’s important to have these killer T-cells in the lung tissue because that’s where the infection was. I want to know how to raise the baseline of these killer CD8 T-cells and help them stay in the airways,” says Yeung. Yeung focuses on how a signalling molecule called “4-1 BB ligand” and “receptor 4-1 BB” communicate to help immune cells move into the memory stage and how this helps them stay in the lung tissue.
Yeung’s supervisor, Tania Watts, a professor in Temerty Medicine’s Department of Immunology, leads a group working to find ways to harness the power of T-cells and lay the groundwork for them to help fight viral villains in new vaccines. Her lab is working to determine how to generate a long-lived immune response in the lung’s mucosal surfaces to one day provide protection with a T-cell vaccine. To do this, the team is studying a group of molecules called the “tumor necrosis factor receptor family.” There are about 30 members of this receptor family, and some may control how many T-cells persist in the lung during a flu infection.
“Lymphocytes disappear from the lung over time, which might be why there isn’t long-term protection from influenza. Is it because the environment in our lungs isn’t conducive to keeping the lymphocytes there? Or would having lots of lymphocytes in our lungs cause a harmful amount of inflammation?,” asks Watts, who holds the Canada Research Chair in Anti-Viral Immunity.
“We want to find out how to get a long-lived immune response in the lung’s mucosal surfaces. Even if we couldn’t completely prevent the flu, if we can minimize the severity, we could save a lot of lives. And a T-cell vaccine would do that,” she says.
While Yeung and Watts explore how to boost T-cells’ superpowers, Aaron Reinke takes another approach to immune memory. Reinke, an associate professor in Temerty Medicine’s Department of Molecular Genetics, is studying how the fungus microsporidia infects a microscopic nematode worm called “Caenorhabditis elegans” or “C. elegans.”
Microsporidia are single-cell parasites that use a harpoon-like appendage to transfer their DNA into their host cells. In addition to infecting nearly all types of animals, many species of these parasites can also make humans sick. Through their research, Reinke’s team is learning how immune memory is passed from one generation to the next.
Over a hundred years ago, scientists first observed the phenomenon of immunity being passed from parents to offspring in lab mice. Then about 20 years ago, they observed it in invertebrate systems like the nematodes that Reinke studies today. As Reinke explains, since nematodes don’t have antibodies, there must be another mechanism working to provide them with protection from the parasitic infection.
Reinke’s lab has shown that infecting the worms with microsporidia creates resistant offspring because there are molecules that prevent the parasite from being able to invade the host cells. Now, they want to identify what generates that immunity and how that information is communicated.
“By looking closely at C. elegans, we can start to understand how immunity is passed down from one generation to the next. Potentially, some of those mechanisms could be relevant in the human immune system. It’s still early, but we’re learning,” says Reinke.