The yearly flu vaccine is the single best method to protect against the flu, which infects up to 35 million people in the U.S. alone every year, but the shot doesn’t protect everyone who receives it. The vaccine’s effectiveness varies from year to year, and researchers estimate it is only between 50 to 67 percent effective in adults under 65. That means that, depending on the year, a third to one half of adults who get the shot won’t mount as strong an immune response as the rest of the population, even though they may still have better protection against the flu virus than if they had never been vaccinated at all. For adults 65 and older, the standard flu vaccine is even less effective, although new, higher-dose vaccines can boost protection in this age group.
So clearly there’s room for improvement. For the first time, researchers have uncovered a set of genes that predicts whether the flu vaccine will work in adults 35 years old or younger.
The prediction, undertaken by a nationwide team of researchers known as the Human Immunology Project Consortium, came to light through a Big Data-scale analysis of more than 32,000 genes from more than 500 people who had received the flu vaccine in different parts of the U.S. during several different flu seasons. The study, published in the journal Science Immunology, looked at adults 35 years old and under, as well as those 60 and older, who had received the vaccine.
That variety of data was important to make sure the researchers were capturing a signature that could apply to a larger population, said a senior author on the study. But the result was a large and complex dataset that required new computational tools to separate the wheat from the chaff.
The analysis pinpointed a set of nine genes (RAB24, GRB2, DPP3, ACTB, MVP, DPP7, ARPC4, PLEKHB2, and ARRB1) linked to the immune response to flu shots, a discovery that could lead to better flu vaccines for those who don’t currently benefit as much from the yearly shot, senior author said and emphasized that results like these don’t mean people shouldn’t bother getting vaccinated. In fact, the opposite is true, even in years that the flu vaccine is less effective.
“There is this thinking that the flu vaccine just doesn’t work, which is just not true,” senior author said. “It can be highly effective in preventing infection, but I think we have a way to potentially improve it further by looking at these baseline responses.”
Those baseline responses could one day let clinicians sort people into two groups: those with a gene signature that shows they will benefit the most from the standard flu vaccine and those without it, who may need a different type or amount of the flu vaccine to boost their protection.
Their findings could be the first step to a personalized flu vaccine, senior author said.
Although the researchers also looked for genes that would predict a vaccine response in older adults — with the hope of pointing to much-needed improvements in this population, which can be more vulnerable to dangerous effects from the virus — they couldn’t find any, senior author said. That might be because there are so few older adults who respond well to the standard vaccine in the first place.
To find the vaccine predictor in younger adults, the researchers looked at 32,034 genes in blood samples taken from several hundred adults — before the study volunteers were vaccinated. They then looked for genes whose activity increased specifically in those volunteers who also showed a better immune response to the vaccine. (Mounting a better immune response is tightly linked to being protected against the infection, senior author said.)
Sifting through that large gene set across several different groups of people yielded the set of just nine genes whose activity increased significantly only in the young adults who would later show a good response to the flu vaccine. Gottardo and his colleagues looked at that same set of genes in older adults, but the collection didn’t predict vaccine response in those 60 and older.
Finding that signature in the first place was only possible by combining the data across multiple different research teams from different institutions, senior author said.
Before this set of genes could be turned into a predictive assay for whether the flu vaccine will work, these results would first need to be validated by other researchers, senior author said. Authors also want to understand the biology behind the link between these genes and the flu vaccine. Some of the genes they found are involved in producing antibodies, the immune molecules that protect against infection, but some are involved in other processes in the body whose tie to vaccination is less clear.
The researchers also saw that the nine genes’ activity stayed constant over the span of a few weeks, but they don’t yet know whether that signature will hold true over a lifetime or whether the genes’ activity could change year to year. This would mean the difference between a one-time test for vaccine response and needing to get a blood draw every year before receiving the flu vaccine. Of course, a research or industry group would need to research and develop such a test — and most importantly, researchers would also have to figure out a vaccination strategy that works better in those who don’t respond well to the current shots.