Metabolic health determines the effectiveness of the flu shot

Metabolic health determines the effectiveness of the flu shot

Metabolic health (including normal blood pressure, blood sugar and cholesterol levels) influences the effectiveness of flu vaccinations. The vaccine is known to be less effective in people with obesity than in people with a healthier body mass index (BMI). However, scientists at St. Jude Children's Research Hospital have found that it is not obesity itself but metabolic disorders that make the difference. In a study published today inNature microbiologistThe researchers found that switching obese mice to a healthy diet before flu vaccination, but not after, completely protected the models from a lethal flu dose, despite BMI.

We found that the vaccines were effective when an animal was metabolically healthy at the time of vaccination. And the opposite was also the case: regardless of what the mice looked like on the outside, if they had a metabolic disorder, the vaccines didn’t work as well.”

Stacey Schultz-Cherry, PhD, corresponding author, St. Jude Department of Host-Microbe Interactions and co-director of the Center of Excellence for Influenza Research and Response

Previous research has shown that 100% of obese mice succumbed to the disease when exposed to the influenza virus, even after vaccination. Contrary to scientists' original expectations, results did not improve when mice vaccinated while obese returned to a healthy weight. These now outwardly healthy mice still all succumbed to the disease when exposed to the real virus. Only switching to a healthy diet four weeks before vaccination drastically improved survival despite a high BMI.

“We were excited to see this effect because obese mice are so susceptible to severe disease and succumbing to infection,” Schultz-Cherry said. “It was impressive to achieve a 100% survival rate with the vaccine, when previously we had only seen a 0% survival rate.” The improved survival rate suggests that researchers have discovered a larger underlying principle that determines the effectiveness of the flu vaccine.

A metabolic disorder affects the immune system

By studying how metabolic function influences the response to flu vaccines, scientists found that poor metabolic health causes immune system dysfunction. T cells, the primary immune cells involved in antiviral responses, were unable to function even when subsequently exposed to the virus in animals that were in an unhealthy metabolic state at the time of vaccination. Even if the animals ate a healthy diet and maintained a normal BMI after vaccination, the anti-flu T cells were “frozen” in this dysfunctional state.

However, a healthy diet before vaccination improved T cell function, leading to a robust anti-flu response upon subsequent exposure.

“In the metabolically healthy mice, the T cells were able to do their job better at the time of vaccination,” said Schultz-Cherry. "It wasn't the number or the type of them that mattered. It was their functional activity. There were a lot of them in the lungs that weren't functioning. The healthy diet made them not functioning properly, just functioning properly." if the change took place before the vaccination.”

The previous healthy diet also improved inflammation. In obese animals, pro-inflammatory cytokines are upregulated. Schultz-Cherry's team found that the models regained lower basal cytokine levels even when they switched to a healthy diet before vaccination.

“A healthy diet reduced some of the systemic meta-inflammation in these animals and they regained some of the epithelial innate immune response,” Schultz-Cherry said. "We saw better signaling from things like interferons, which we know are problematic in obesity, and in general we saw the immune system start to function as it should."

Improving metabolic health can improve the effectiveness of the flu vaccine

"What we found and emphasize is that it's not the obesity phenotype that matters; it's more about metabolic health," Schultz-Cherry said. “It is metabolic health at the time of vaccination that really makes the difference.”

The study was limited to mice, but opens up research opportunities to improve the effectiveness of the flu vaccine in humans. The results suggest that methods to improve metabolic health can also improve subsequent flu vaccinations. Given the recent introduction of metabolism-enhancing drugs, particularly glucagon-like peptide-1 (GLP-1) agonists, the possibility of a cooperative effect may exist.

"We don't know for sure, but if the result of using GLP-1 drugs is weight loss and improved metabolic health, we assume it will help," Schultz-Cherry said. “But we know we can better protect our vulnerable populations, and this study is a start to understanding how.”

Authors and funding

The study's co-first authors are Rebekah Honce, formerly of St. Jude, and Ana Vazquez-Pagan, formerly of the St. Jude Graduate School of Biomedical Sciences.

The study's other authors are R. Chris Skinner, University of Vermont, Brandi Livingston, Alexandra Mandarano, Benjamin Wilander, Sean Cherry, Virginia Hargest, Bridgett Sharp, Pamela Brigleb, Ericka Kirkpatrick Roubidoux, Lee-Ann Van de Velde, Maureen McGargill and Paul Thomas, St. Jude.

The study was supported by grants and contracts from the National Institute of Allergy and Infectious Diseases (HHSN27220140006C, 75N93019C00052, 75N93021C00016, F31AI161986, R01 AI140766-03 and 32AI106700-07) and ALSAC, the fundraising and awareness organization of, supports St. Jude.

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