Study details age-related differences in flu vaccination response

Feb 6, 2013 (CIDRAP News) – A detailed inventory of antibodies in the blood of people before and after flu vaccination found that the number of antibody types shrink with age, suggesting that vaccines may work differently in older people, a research team reported today.

The immune systems of older people don't respond to flu vaccination as well as those of younger people, and people age 65 and older are at greater risk of serious complications from the disease. Scientists haven't completely pieced together why seniors have a less robust immune response to flu vaccine, but new studies are starting to shed some light on age-related antibody changes that may play a role.

In the current study, researchers based at Stanford University analyzed blood samples from 17 volunteers from different age-groups who were immunized against flu with the 2009 or 2010 seasonal flu vaccines. Their findings appear today in Science Translational Medicine.

The group noted that it's difficult to measure and analyze the human antibody repertoire, because the genome for each B cell encodes a distinct, personalized antibody sequence, the antibody repertoire changes over time, and antibody sequences are highly similar.

To address the challenges. the scientists used high-throughput long-read sequencing and analyzed 5 million antibody heavy chain sequences, which allowed them to characterize the sequences, determine lineage structures, and measure age- and antigen-related mutation activity.

The volunteers were recruited from three age-groups: children (ages 8 to 17 years old), young adults (ages 18 to 30), and older people (ages 70 to 100). The cohort included three sets of twins in the youngest age-group to allow researchers to analyze the antibody profiles of people with identical genetic backgrounds. Subjects were randomly vaccinated with either trivalent inactivated influenza vaccine (TIV) or live-attenuated influenza vaccine (LAIV), although the older group could only receive TIV.

Blood samples were collected from each person at three points: right before vaccination, at 7 or 8 days after vaccination, and 28 days after vaccination.

The researchers found significant differences in antibody composition by different age-groups. For example, the relative percentage of immunoglobulin M (IgM) sequences dropped after vaccination in all volunteers except one and reduction in IgM usage decreased with age.

These findings are consistent with the hypothesis that older people are more likely to use memory B calls than naive NB cells to respond to flu vaccination, according to the study.

Though the results lend support to the theory that flu vaccines may work differently in seniors, the authors noted in summary e-mailed to journalists that the findings don't suggest that older people should stop getting vaccinated. They suggested that elderly people avoid activities that expose them to flu viruses and seek medical care when the first symptoms of flulike illness surface.

Jiang N, He J, Weinstein JA, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med 2013 Feb 6;5(171) [Abstract]

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