Gene variant linked to robust flu vaccine response

Targeting immune signaling protein may offer a way to increase protection

Variant forms of a gene might tip off doctors to people who are naturally more or less likely to benefit from a flu vaccination. A new study of the gene variants’ effect also suggests a novel approach to boosting immunity, researchers say, that could be particularly helpful in elderly or immune-compromised people who generate subpar responses to vaccines.

Variations in the interleukin-28B gene, which encodes an immune system signaling protein, might account for some of the differences in protection seen among people getting the flu shot. Some harbor a form of the gene that induces a cell to produce less of the signaling protein. That may be good because lab tests show that this underproduction gins up a stronger antibody response from flu vaccination, researchers report in the December PLoS Pathogens.

“This is a very provocative finding and an interesting observation,” says Octavio Ramilo, a pediatric infectious disease doctor at Ohio State University in Columbus. But it is an early-stage finding that would need to be borne out in tests in animals and people to establish that revving up antibody production by undercutting interleukin-28B is a net gain — and doesn’t come at the expense of some other form of immune protection, he says.

The researchers tested immune cells from the blood of 196 immune-compromised transplant recipients who had recently been vaccinated against the flu. Most had the common form of the IL-28B gene. Those with the variant form were nearly twice as likely as their counterparts to develop enough antibodies to trigger a strong response against flu.

In immune cells obtained from 49 vaccinated healthy volunteers, the scientists added a protein particle designed to block the signaling action of IL-28B protein, and antibody production increased substantially. In a separate test, when the researchers added extra IL-28B protein to a lab dish of similar cells, antibody production fell.

The results suggest a peptide-based drug that blocks IL-28B signaling might thus increase the efficacy of flu vaccination, but it would first need to go through testing, says study coauthor Deepali Kumar, an infectious disease doctor at the University of Toronto.  

Other researchers have looked for genetic traits that might explain the wide range of responses people generate to flu vaccination. John Belmont, a pediatrician and geneticist at Baylor College of Medicine in Houston, and his team reported in eLife in 2013 that at least 20 genes appear to come in variant forms that influence such responses. These different forms might provide clues to the variability in responses to the vaccine, but any effect would probably stem from a combination of traits, he says. “It is not likely that testing a single [genetic] variant would allow one to predict who will be a poor responder to flu vaccine. That would count as an extraordinary claim and require extraordinary evidence to support it,” Belmont says.

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