Vaccines Fail to Deliver Protection from Severe Flu Infections in Obese Mice

First evidenced in the 2009 H1N1 pandemic, obesity is a high risk factor when it comes to the development of severe influenza-related infections, which makes receiving effective vaccination imperative. However, in a study in mice, led by St. Jude Children’s Research Hospital, researchers found that vaccines that include adjuvants did not protect obese mice from influenza infections as they did their lean counterparts. These results, published in mBio, are concerning for obese humans who are also known to be high-risk for severe influenza infections.

Stacey Schultz-Cherry, PhD, a member of the St. Jude Department of Infectious Disease, said, “This is the first study to show that current strategies to bolster the effectiveness of flu vaccines protected lean mice from serious illness but fell short of protecting obese mice from infections.”

According to the World Health Organization (WHO), worldwide obesity has more than doubled since 1980. A total of 1.9 billion adults, 18 years or older, were overweight, and of these, 600 million were obese in 2014. Obesity has become a worldwide epidemic and these individuals are at higher risk for flu-related complications such as hospitalization and death, which makes vaccine efficacy paramount.

When speaking on the need for vaccine efficacy, Schultz-Cherry said, “There is a critical public health need to translate these findings to humans and understand vaccine response in this growing segment of the population.”

In the study, researchers hypothesized that the addition of an adjuvant, a substance that works to enhance the body’s immune response, to an influenza vaccine would protect obese mice from the infection by improving their neutralizing antibody responses. The study found that even the adjuvanted vaccine (A[H7N9]) increased neutralizing antibody levels, as well as nonneutralizing antibody levels compared to the vaccine alone. However, the antibody levels of obese mice overall were lower following the vaccination, showing lower levels of neutralizing antibodies and higher levels of the virus, according to the news release.

Schultz-Cherry explained, “The addition of adjuvants to the vaccines led to levels of neutralizing antibodies in both the lean and obese mice that have been considered to be protective. Surprisingly, that did not translate into protection from flu infection or fatal disease in obese animals.”

When speaking on the implications of these findings, Schultz-Cherry said that when it comes to obese individuals, these results suggest that even if their blood antibodies reach protective levels, they may still be at risk for flu infections.

In another test, the researchers at St. Jude Children’s Research Hospital administered 4 times the amount of the dose of A(H7N9) which resulted in increased immune system response in both lean and obese mice, however, still failed to protect the obese mice from death by flu infection.

Erik Karlsson, PhD, a staff scientist in the Schultz-Cherry laboratory said, “That suggests the problem lies with the immune response of the obese animals rather than the antibodies themselves.” This means that obese mice may be more susceptible to the virus. Schultz-Cherry said that when it comes to obese mice, the virus penetrates more deeply into their lungs, making it more difficult for them to repair the damage caused, according to the news release.

Research continues at St. Jude as well as in the rest of the healthcare community, as researchers strive to develop vaccines that can safely and more effectively fight flu infections, particularly for those who are at a higher risk for developing these infections, such as pregnant women, the elderly, and obese individuals.