La Jolla study: Whether the flu shot will protect you is in your blood

La Jolla Institute for Immunology scientists find that a person’s past vaccine response, not age, sex or vaccine dose, is the best predictor of future vaccine responses.

How your body responded to past flu vaccines predicts your response to the upcoming flu vaccine, according to a new study by scientists at La Jolla Institute for Immunology.

“Some people have incredibly strong responses to annual flu vaccines, and some people don’t respond at all,” said Tal Einav, Bodman Family Assistant Professor at LJI and member of LJI’s Center for Vaccine Innovation.

Einave and his colleagues shared their findings in a recent eBioMedicine study, after developing a machine learning model to analyze massive datasets from multiple flu vaccine studies.

Using their model to spot trends across 20,000 antibody responses from influenza studies conducted between 1997 and 2021, researchers discovered that a person’s responses to prior flu strains is a better predictor of future responses than a person’s age, sex, geographic location or the vaccine dose they receive.

“Many studies have shown that age has an effect. We have just shown that it is a very small effect, whereas you can get far better predictions with antibody responses that can be measured from your blood,” Einav said.

The influenza virus acquires a few mutations each year, so researchers don’t focus on a person’s antibody response to past flu strains but instead consider the response to the currently circulating strains.

The new LJI study shows the importance of looking back in time and measuring the immune cells and antibodies produced by the body after a vaccine or viral infection.

Because influenza mutates quickly and flu vaccine formulations change each year, scientists can distinguish between an antibody response to viruses from this year, last year, or even earlier. By measuring all of these strains, researchers can assemble a reliable, chronological record of a person’s immune responses to the flu from each year.

“Blood doesn’t forget,” said Einav.

The researchers found that strong vaccine responders had “jagged” antibody titers that would be high in one year, low against the prior year’s strain, high again the year before that, and continue in this fashion. On a timeline, these peaks create a regular pattern that resembles a row of shark teeth, where each peak indicates a strong response to that specific flu strain.

These yearly fluctuations, or jagged peaks, are a useful “signature” of an immune system on high alert, Einav said.

Einav and his colleagues are now looking for immune system markers that might show whether certain vaccine formulations can boost immune cell reactions in weak responders in a step toward more personalized and effective vaccines.

“Our hope is to be able to predict for each person what their response is going to be for each different vaccine,” said Einav.