The yearly flu shot is becoming less effective over time. One possible reason is that the vaccine may not work as well for people who are obese compared to those with a healthier weight, and the number of obese individuals is increasing. Studies have found that when mice were switched to a healthy diet four weeks before getting the flu shot, they were 100% protected from the flu later on, even though they were still obese.
Researchers at St. Jude Children’s Research Hospital discovered that improving the metabolic health of obese mice before they were vaccinated, not after, helped protect them from the flu virus.
rnrnMetabolic health, which includes normal blood pressure, blood sugar, and cholesterol levels, among other factors, is known to impact the effectiveness of influenza vaccinations. It has been observed that vaccination is less effective in individuals with obesity compared to those with a healthier body mass index (BMI). However, scientists at St. Jude Children’s Research Hospital have discovered that it is not obesity itself, but rather metabolic dysfunction, that makes the difference. In a study recently published in Nature Microbiology, the researchers found that switching obese mice to a healthy diet before flu vaccination, but not after, completely protected the models from a lethal dose of flu.
Despite BMI, the vaccines were effective in metabolically healthy animals, according to Stacey Schultz-Cherry, PhD, corresponding author and co-director of the Center of Excellence for Influenza Research and Response. Conversely, mice with metabolic dysfunction did not respond as well to the vaccines, regardless of their outward appearance.
Previous studies revealed that even after vaccination, 100% of obese mice died when exposed to the influenza virus. This was contrary to the scientists’ initial expectations.The study found that even though obese mice were vaccinated and returned to a healthy weight, they still did not have better outcomes. These mice appeared healthy, but they still got sick and died when they were exposed to the real virus. The only thing that improved their chances of survival was switching to a healthy diet four weeks before getting vaccinated, even though they still had a high BMI.
According to Schultz-Cherry, the lead researcher, this was an exciting discovery because obese mice are usually so susceptible to severe illness and are likely to die from the infection. Achieving 100% survival with the vaccine in mice that previously had 0% survival was impressive. The improved survival rates indicate that the researchers may have found a significant discovery.
One of the key factors that determines how well the influenza vaccine works is the underlying principle of metabolic dysfunction affecting the immune system.
When researchers looked into the connection between metabolic function and the body’s response to the influenza vaccine, they discovered that poor metabolic health leads to immune system dysfunction. In particular, T cells, which play a crucial role in fighting off viruses, were unable to function properly in animals with poor metabolic health at the time of vaccination, even when they were later exposed to the flu virus. Even when these animals improved their diet and maintained a healthy weight after vaccination, the anti-flu T cells remained stuck in a dysfunctional state.
However, prior to vaccination, a nutritious diet enhanced the functionality of T-cells, leading to a strong immune response against the flu virus.
According to Schultz-Cherry, “The metabolically healthy mice had T-cells that were more effective at the time of vaccination. It wasn’t about the quantity or type of T-cells, but rather their functional activity. There were plenty of T-cells in the lungs, but they were not functioning properly. The healthy diet was able to activate their proper functionality, but only if the switch occurred before vaccination.”
In addition, the pre-vaccination healthy diet also reduced inflammation.A study found that obese animals have higher levels of pro-inflammatory cytokines. The researchers also discovered that when these models switched to a healthy diet before being vaccinated, their cytokine levels returned to normal. According to Schultz-Cherry, “A healthy diet reduced some of the overall inflammation in these animals, and they also showed improved immune responses. We observed better signaling of interferons, which is typically impaired in obesity, and overall, the immune system began to function more effectively.”
The study suggests that improving metabolic health could potentially enhance the effectiveness of influenza vaccines.s
According to Schultz-Cherry, the focus should not be on the physical characteristics of obesity, but rather on metabolic health. She emphasized that it is the state of metabolic health at the time of vaccination that really makes a difference.
Although the study was only conducted on mice, it does present new opportunities for research aimed at enhancing the effectiveness of influenza vaccines in humans. The results indicate that improving metabolic health could also lead to improved response to influenza vaccinations. With the recent development of drugs to improve metabolism, such as glucagon-like peptide 1 (GLP-1) agonists, there is potential for collaboration in this area.
“Even though we can’t say for certain, if the result of using GLP-1 medications leads to weight loss and improved metabolic health, we might assume that it could be beneficial,” Schultz-Cherry stated. “However, we do know that we can improve the protection of our vulnerable populations, and this research is a step toward understanding how.”
Writers and financial support
The primary authors of the study are Rebekah Honce, previously of St. Jude, and Ana Vazquez-Pagan, formerly associated with the St. Jude Graduate School of Biomedical Sciences.
Other contributors to the study include R. Chris Skinner from the University of Vermont, and Brandi Living.Rebekah Honce, Ana Vazquez-Pagan, Brandi Livingston, Alexandra H. Mandarano, Benjamin Wilander, Sean Cherry, Virginia Hargest, Bridgett Sharp, Pamela Bridleb, Ericka Kirkpatrick Roubidoux, Lee-Ann Van de Velde, Maureen McGargill, and Paul Thomas. The study received support from the National Institute of Allergy and Infectious Diseases and ALSAC, the fundraising and awareness organization of St. Jude.
