New research led by investigators at St. Jude Children's Research Hospital has uncovered that obese mice are not protected against influenza infections by vaccines that include adjuvants—raising concerns about vaccine effectiveness in obese humans who are known to be at an increased risk for severe flu infections. These recent findings come amid ongoing concerns about flu pandemics launched by avian flu viruses and the global rise of obesity.
“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,” explained senior study author Stacey Schultz-Cherry, Ph.D., a member of the St. Jude Department of Infectious Diseases and deputy director at the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds.
The World Health Organization has estimated that 10% of adults worldwide and 42 million children under the age of five now qualify as obese. Obesity leaves individuals at increased risk for flu-related complications, including hospitalization and death. “There is a critical public health need to translate these findings to humans and understand vaccine response in this growing segment of the population,” Dr. Schultz-Cherry noted.
Vaccination remains the most effective flu prevention strategy and a key element in pandemic flu preparedness. Researchers are continually developing more effective flu vaccines, particularly for high-risk groups, including the elderly, pregnant women, and obese individuals. These new strategies include increasing the vaccine dose and adding substances called adjuvants to vaccines to boost the immune response.
“We tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge,” the authors wrote. “Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice.”
The findings from this study were published recently in mBio in an article entitled “Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination.”
The investigators used vaccines prepared from killed viruses that are the basis of flu shots. The vaccines targeted an influenza A H1N1 seasonal flu strain as well as influenza A H7N9, a virus considered to have the potential to trigger a human pandemic. Researchers looked at the immune response to vaccination in lean and obese mice, including how vaccine dose and different adjuvants impacted that response. Both methods have been used to improve vaccine effectiveness in older adults and other high-risk groups.
Interestingly, the researchers found that while adjuvants improved the immune response to vaccinations in both lean and obese mice, the overall immune response was reduced in the obese animals compared to their lean counterparts. Following vaccination, the obese mice had lower antibody levels, including lower levels of neutralizing antibodies, and higher levels of the virus.
Additionally, lean mice that received vaccines with adjuvants were protected from severe flu infections. Obese mice, however, were not.
“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 the obese animals,” Dr. Schultz-Cherry remarked.
This data would suggest that obese individuals may be at risk for flu infections even if their blood antibodies reach what have been considered protective levels. A four-fold increase in the dose of influenza A H7N9 vaccine bolstered the immune response in both lean and obese mice, but failed to protect the heavier animals from flu-related deaths.
Because protective antibodies from lean mice also failed to guard obese mice from flu infections, Dr. Schultz-Cherry surmised that “the problem lies with the immune response of the obese animals rather than the antibodies themselves. The virus penetrates more deeply into the lungs of obese mice, and the animals seem to have a more difficult time repairing the damage.”