Cell: new research reveals why it's so difficult to develop a universal influenza vaccine

December 28, 2019 / BIOON / - -- every year, we are reminded to go to the pharmacy for influenza vaccination Why can't we have flu vaccines that provide long-term protection like measles or polio vaccines? This is because the influenza virus continues to evolve, so the immune response we set up in the first year may not work in the second year or even in the influenza virus we infected in that year As a result, the flu virus remains dangerous: last year, in the United States alone, it killed more than 60000 people In a new study, researchers from Rockefeller University in the United States revealed why it is so difficult to create a universal vaccine that can prevent all types of influenza viruses: the immune system's immune response to a new influenza virus variant is built from scratch, mainly by using immune cells that have no memory of the virus, rather than improving the response to previous ones Influenza virus version of immune memory The relevant research results were recently published in the Journal of cell, and the title of the paper is "restricted closeness and limited German Center reentry characterize memory B cell reactivation by boosting" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.11.032 "If we can figure out how to help the immune system build immune memory on the basis of existing knowledge, we can develop better vaccines for highly evolved viruses such as influenza virus, HIV and hepatitis C virus," said Gabriel D victora, an assistant professor at Rockefeller University and the corresponding author of the paper Frustrated immune memory victora and his team explored immune cell behavior in mice exposed to influenza vaccines for the first and second time Specifically, they studied B cells, the white blood cells that release antibodies The response of antibodies is to attack invaders such as viruses or to tag them so that they can be attacked by other cells During infection or vaccination, B cells enter the germinal center of lymph nodes, where they mutate many times until they can target new invaders "It's like a training camp," victora said B cells have poor performance when they enter the germinal center, and they have very good performance when they leave the germinal center, so as to release better antibodies that are more closely bound to their targets " These very good B cells are cell memories in the immune system that can release antibodies that bind to a part of the invading virus Ideally, these B cells would return to the germinal center the next time the body encounters a virus or vaccine, and evolve more complex antibodies to better target slightly different versions of the virus, eventually producing broad neutralizing antibodies that the so-called virus cannot escape That's what people need to make universal vaccines "Our idea is that by vaccinating over and over again, you can keep recalling memory cells to germinal centers so that they can go through multiple evolutions until they become super B cells, which is what is needed to provide a universal influenza or HIV vaccine," victora said But instead of seeing B cells return to the germinal center, the researchers found something different They used fluorescent dyes to genetically label the germinal centers of mice at the first vaccination, so they could track the behavior of their offspring at the second vaccination To their surprise, more than 90% of the B cells entering the germinal center at the time of the second vaccination were unlabeled, indicating that they were newcomers Genetic analysis also showed that these cells did not undergo the mutation process commonly experienced by B cells in the germinal center, which further indicated that they were the first to appear at this site But most of the veterans in the boot camp don't exist Of the hundreds of B cells that enter the germinal center at the time of the first vaccination, only a few can return to the germinal center at the time of the second vaccination, but most of them can combine with the invading virus It seems that only a few selected B cells will return to the germinal center at the time of the second vaccination If further research shows that these findings are the same in humans, it will have an impact on vaccine design To get strong B cells, scientists need to understand what prevents them from returning to training camps "If we can understand the bottlenecks that don't allow these cells to re-enter, then this may help us find a way to circumvent them, making the method of repeat vaccination easier to work," victora said This will give these cells the opportunity to go through many rounds of mutations that they need to undergo in order to obtain antibodies that target all variants of a virus such as influenza or HIV (BIOON Com) reference: 1 Luka mesin et al Restricted closeness and limited German Center reentry characterize memory B cell reactivation by boosting Cell, 2019, doi:10.1016/j.cell.2019.11.032 2.New clues about why a universal flu vaccine is so elusive https://medicalxpress.com/news/2019-12-clues-universal-flu-vaccine-elusive.html