Flu vaccinations less likely to be effective in obese mice

Results of the study could mean that we need to alter vaccinations in humans.

Obesity comes with a myriad of health implications, including a greater susceptibility to flu infections. However, a study released today by mBio has found that influenza vaccinations do not protect obese mice from severe cases of the flu, which could have implications for obese humans. The study’s author, Stacey Schultz-Cherry, told us more.

RG: Could you explain your study and the significance of your results?

Stacey Schultz-Cherry: The 2009 pandemic provided the first evidence that obesity could be a risk factor for developing severe flu infection. Therefore, the prevention of infection by vaccination is of utmost importance for this high-risk group. Our previous studies showed that vaccinated obese animals had decreased levels of neutralizing antibodies as compared to lean animals.

That's what spurred us to look into whether adding an adjuvant to the vaccine increase the antibody response in obese mice. While the adjuvanted vaccine did increase both neutralizing and non-neutralizing antibody levels, obese mice had decreased responses in comparison to lean mice. Additionally, obese mice were not protected against flu even though they reached a level of vaccine response considered “protective.” Even increasing the amount of protein in the vaccine, an approach successfully used for improving vaccine responses in the elderly, did not protect obese mice from flu infection. Given the global obesity epidemic, our findings highlight the need to improve flu vaccines for this high-risk population.

Flu vaccines tested on obese mice. Credit: Wikimedia Commons.
Flu vaccines tested on obese mice. Credit: Wikimedia Commons.

RG: How did you ensure that the mice were obese? Could this have influenced the results you found?

Schultz-Cherry: We primarily used genetically obese mice in this study. They lack the hormone leptin and basically have no control of their appetite, hence will eat until they become extremely obese. They are a model for morbid obesity. However, similar results were obtained with mice fed high-fat diets, which are more representative of overweight and obese populations.

RG: Why did you decide to study this?

Schultz-Cherry: We knew that obese mice, and potentially humans, were at increased risk for developing severe flu infection. Thus, we wanted to find a way to protect them. Studies in vaccinated adults strongly suggested that overweight or obese adults had a more rapid loss of neutralizing antibody levels post-vaccination as compared to average weight people. However, there is no way to understand how this would impact protection from infection. Developing this animal model allowed us to address that question and evaluate whether we can bolster the response and better protect our high-risk population.

RG: How could the results of your study translate to humans?

Schultz-Cherry: Our goal is to understand why the obese mice aren’t protected and how we can improve their protection, and then translate this information to people.

RG: Do you have any insight into how the influenza vaccine could be made more effective for obese mice?

Schultz-Cherry: We could try different adjuvants, different routes of administration (microneedle or subdermal rather than intramuscular), increase the number of boosts, and even the types of vaccine. There are many options, but we still need to understand why they aren’t protected from flu infection even when they have protective antibodies. We have also discussed what would happen if the mice lost weight – would they now be protected?

RG: Have studies looked into how effective other vaccinations are in obese mice?

Schultz-Cherry: Unfortunately, the impact of obesity on vaccine responses is not well understood. The first study to describe a relationship between vaccine response and obesity was published in 1985 by Weber et al. They found that a higher BMI was the single best predictor of vaccine failure against hepatitis B. Since then, other studies have also shown an association between obesity and poor antibody response to hepatitis B vaccines. Aside from hepatitis, some associations have also been made for decreased responses to standard tetanus vaccines in obese children. Yet, overweight and obese people are not typically included in “healthy” people vaccine trials so the true impact of obesity on vaccination against different microbes is unknown.

RG: What are the next steps in this research?

Schultz-Cherry: As mentioned before, we want to understand why obese mice and ultimately people have decreased vaccine responses and how we can overcome this. Also, what does this actually mean in terms of susceptibility to flu or other infections? However, we don't want our study to discourage people from getting the flu shot.

Image of influenza virus credit Sanofi Pasteur via flickr.