Research provides insights on how to build better flu vaccines

The flu season occurs every year, like a clockwork. Annual flu vaccination is an important part of public health efforts to control flu, but the effectiveness of the vaccine is not well known, somewhere between 40% and 60% of the typical year Is falling.

An increasing body of evidence suggests that the history of exposure to influenza viruses can undermine the effectiveness of annual influenza vaccines. Partial immunity developed during previous flu seasons through natural infection or vaccination may interfere with the body’s response to the new vaccine. As such, vaccination largely raises awareness of older influenza strains, but rarely creates the ability to fight new strains.

Now, a team led by researchers at the University of Washington School of Medicine in St. Louis has developed an approach to assess whether the vaccine activates the types of immune cells required for persistent immunity against the new influenza strain. Using this technique, researchers have shown that the influenza vaccine can elicit antibodies that protect against a wide range of influenza viruses, at least in some people. The findings, published August 31 in the journal Nature, may support efforts to design improved influenza vaccines that provide protection not only against old influenza viruses, but also against new influenza viruses.

“Every year, about half of the adult population of the United States is vaccinated against influenza,” said lead author Ali Elbedy, assistant professor of pathology and immunology at the University of Washington. “It’s necessary for public health, but it’s incredibly expensive and inefficient. What you need is a one-time flu shot, but not yet. For us to make a better vaccine , Anything that helps us understand how immunity develops in the context of previous exposures is important.”

The key to long-lasting immunity lies in the lymph nodes, the very fine organs of the immune system throughout the body. Often overlooked in healthy people, immune cells actively interact and multiply, resulting in swollen lymph nodes and tenderness during infection.

When a person is first exposed to the virus by infection or vaccination, immune cells capture the virus and carry it to the nearest lymph nodes. There, the virus is presented to so-called naive B cells, maturing them and initiating the production of antibodies to fight the infection. When the virus is successfully routed, most immune cells that participate in the battle die, but some continue to circulate in the blood as long-lived memory B cells.

When a person is exposed to the virus a second time, memory B cells quickly reactivate, bypassing naive B cells and restarting antibody production. This quick response will quickly protect people re-infected with the exact same strain of virus, but will give people who receive a vaccine designed to build immunity to a slightly different strain, like the annual influenza vaccine. Is not ideal.

“When our influenza vaccine targets memory cells, those cells respond to parts of the virus that have not changed from previous influenza strains,” Ellebedy said. “Our goal is to bring our immune system up to date with new strains of influenza. This year, we want to focus our immune response on different parts of the virus.”

In order to obtain decades of immunity to the new strain, influenza strains from the vaccine need to be delivered to the lymph nodes, where they train a new set of naive B cells, especially a tailored long-lived memory B To recognize the unique features of vaccine strains that can be used to induce cells.

To find out what happens in the lymph nodes after influenza vaccination, Elbedy collaborated with co-author Associate Professor Rachel Presty and Washington University Radiology Professor Charlene Tiffey. Presti led a team of Infectious Diseases Clinical Research Units to coordinate blood and lymph node sampling from healthy volunteers before and after vaccination. Based on ultrasound images, Teefey carefully extracted so-called germinal centers, which carry immune cells from the underarm lymph nodes of eight healthy young volunteers vaccinated with the 2018-19 tetravalent influenza vaccine. The vaccine was designed to protect against four different strains of influenza virus. Immune cells were extracted 1, 2, 4 and 9 weeks after vaccination.

Ellebedy and colleagues analyzed immune cells in the germinal center and found one that was activated by vaccination.

In three volunteers, we show that both memory and naive B cells in the lymph nodes respond to the vaccine strain, and the vaccine initiates the process of inducing long-term immunity to the new strain.

“Our research shows that the influenza vaccine can infect both types of cells in the germinal center, but we don’t yet know how often it happens,” Elbedy said. Stated. “But the effectiveness of the influenza vaccine is hovering about 50%, so it probably won’t happen as often as we would like. It promotes a strategy that boosts germinal centers as a step towards a universal influenza vaccine.” Brings out the importance of that.”

Reprinted courtesy of the University of Washington School of Medicine in St. Louis.