How Genes Affect Your Flu Vaccines

Each year, 132 million Americans flock to doctors’ offices, pharmacies, and clinics for flu shots. With the onset of “flu season” each year, 41% of the population opts to get vaccinated. Currently, flu shots are the most effective way to protect against infection. Despite this, they are only about 60% effective in adults over the age of 65.

Why does the flu vaccine work for some, and not others? The answer, according to a recent study, may lie in our genes. Dr. Albert Shaw led scientists at Yale University and four other research centers to find that certain genes correlate to stronger immune responses. This discovery paves the road for further genetic research and provides insight into the future of vaccination.

“We set out to study why people respond differently to the vaccines. We used the flu vaccine because it is very commonly used throughout the country and you can collect a large number of patients,” said Ruth Montgomery, co-author of the study and associate professor of medicine at the Yale School of Medicine. As Montgomery implied, an important aspect of the study is its size. The genetic data used came from four independent institutions. In total, over 500 individuals participated in the study. The data spans five years of flu vaccination seasons. In combination, these factors make the conclusions of the study more reliable.

“A big part of our study was comparing responses to vaccination with younger and older people. In general, older people have a much less efficient and successful response to vaccination,” Montgomery said. The ages of the participants fell into two groups: either under 35 or above 60 years old. Interestingly, the results for the study differed between the two age groups. The cluster of genes, or “signature,” that correlated to a stronger immune response in younger people did not help the older group. Similarly, the beneficial signatures for the older group did not prove significant to the younger group. “The older people who respond use different genes and cellular pathways than the younger people who respond,” said Montgomery. This means that our immune responses to vaccination change with age, a potential subject for further investigation.

The researchers found the genes that influenced immune response by examining the younger people that did not respond well to vaccination. Nine individual genes and three sets of co-expressed genes were found to impact response to the flu vaccine. “The beauty of this study was combining those young non-responders across a number of different universities and research programs, and using computational tools to try to understand what might lead to a poor vaccine response in a young healthy donor,” said Montgomery.

Montgomery cites much of the study’s success to our increased ability to use computational processes to analyze biological data. Researchers gathered 47,000 RNA transcripts, a form of genetic information in our cells, from each patient. With over 500 participants in the study, this amounts to over 23 million transcripts in total. Without the aid of computer algorithms, this massive amount of data would be impossible to process. With the bioinformatics analysis led by Dr. Steven Kleinstein, researchers could synthesize the data and make significant conclusions.

The results of this study point to possible innovations in vaccination. With the knowledge that older people process vaccines differently from younger people, scientists may develop different methods to boost the effectiveness of vaccines for older people. “It is possible for some sort of therapeutic approach to boost those immune responses, or perhaps with a better understanding of the pathways we can modify what goes into the vaccination for older people,” Montgomery said.

Since the study only examined the flu vaccine, scientists are not yet sure if these genes help in immune responses to other vaccines. “It’s not always clear whether the results from this study will apply to responses to other vaccines, so that would require more study to understand,” she said. All in all, the work of these collaborators provides exciting insight into the genetics behind immune response, and also opens new doors for future research on vaccines.