Obesity outweighs antibody responses generated by an aduvanted H7N9 influenza vaccine and fails to protect mice from influenza infection

Obesity is a risk factor for developing severe influenza infection making vaccination of utmost importance for this high-risk population. Yet, vaccinated obese animals and adults have decreased neutralizing antibody responses. We tested the hypothesis that addition of a squalene-based adjuvant to an influenza H7N9 vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Adjuvanted vaccine increased both neutralizing and non-neutralizing antibody levels as compared to vaccine alone; however, obese mice were not protected from lethal H7N9 challenge. Increasing the antigen dose affords no added protection and decreasing the viral dose did not fully mitigate the increased mortality seen in obese mice. Although obese mice did mount virus-specific antibody responses; both the breadth and the magnitude of the response was decreased as compared to lean mice. Furthermore, antigen microarrays spotted with overlapping 20mer peptides (with 15 overlap) of the hemgaluttinin and neuraminidase H7N9 vaccine strain revealed that lean mice generated stronger and broader antibody responses to the H7 HA and N9. Interestingly, several specific antigens that were targeted in lean mice were not targeted by the obese mice, including some located around the sialic acid recptor binding domain. Overall, these studies highlight that while adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health.