A common paradox in immunology is that those groups who more readily require vaccination tend to be the ones for whom the treatment is less efficacious, and until recently scientists were unclear why. Now, researchers from Emory University and the University of California, San Diego have taken a systems biology approach to answering two main questions that address this incongruity: what factors inhibit strong responses to seasonal flu vaccines in the elderly and why do anti-flu antibodies last longer after vaccination in some people?
The research teams analyzed blood samples from over 400 volunteers that received seasonal flu vaccines and subsequently tracked patterns of gene expression for strong immune responses in volunteers' blood across five consecutive seasons from 2007 to 2011.
“We provide novel evidence of a potential connection between the baseline state of the immune system in the elderly and reduced responsiveness to vaccination,” stated co-senior study authors Shankar Subramaniam, Ph.D., of the University of California, San Diego, and Bali Pulendran, Ph.D., of Emory University. “By providing a more complete picture of how the immune system responds to vaccination, our findings may help guide the development of next-generation vaccines that offer long-lasting immunity and better protection of at-risk populations.”
In previous studies from Dr. Pulendran’s group, the investigators were able to define molecular signatures in blood cells a few days after vaccination. The team found that the molecular signatures could predict the strength of the immune response weeks later.
“Until this study, we didn't know whether those signatures would be similar in diverse human populations or across multiple seasons,” Dr. Pulendran explained. “Our results indicate that certain conserved elements of such signatures are indeed similar in the young and elderly, as well as across multiple seasons.”
The scientists also identified a distinct molecular signature in volunteers when their antibody levels stayed relatively high for several months after vaccination, which could guide efforts to design long-lasting vaccines.
The findings from this study were published recently in Immunity through an article entitled “Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures.”
The investigators found that people older than 65 tended to have weaker antibody responses to vaccination, yet there were common elements of molecular signatures that predicted strong antibody responses in younger and older volunteers.
However, the elderly vaccinated volunteers had stronger signatures from monocytes and natural killer cells—immune cells that are not directly involved in antibody production— both at baseline and after vaccination. The researchers felt this was indicative of a potential connection between the baseline state of the immune system in the elderly and reduced responsiveness to vaccination.
Furthermore, a majority of volunteers, both young and old, showed a substantial drop in the levels of anti-flu antibodies within six months of vaccination. The amount of antibody decrease, however, varied from person to person.
“Surprisingly, the signatures capable of predicting antibody responses at four weeks did not correlate with the longevity of antibody responses at six months or a year,” Dr. Pulendran noted. “Rather, a distinct signature was found to correlate with longevity.”
“Together, these results suggest potential mechanisms by which changes to the innate response in the elderly may result in diminished antibody responses to vaccination,” added Dr. Subramaniam.
Following the peak of an immune response to a vaccine, most of the antibody-producing cells from the blood are diminished, but some find a permanent home in the bone marrow, waiting for the next time they are needed to mount a rapid immune response to foreign antigens. The longevity signature appears to be connected to this process.
“We are currently extending the results of this study to other vaccines to determine whether the signatures of influenza vaccination can be used to predict immune responses to other vaccines, and if, indeed, there is a universal biomarker of antibody responses to vaccination,” Dr. Pulendran stated.
While encouraged by their findings, the researchers urged caution against over-interpretation of their findings.
“This is obviously a complex problem, and the study reveals responses that are averaged across populations,” Dr. Subramaniam said. “As is true in every medical diagnosis, prognosis, and treatment, there is a distribution of responses with a majority conforming to the mean predicted response. So the important thing for the general audience to recognize is that there will be exceptions and variations.”